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Growth hormone (GH) action in the brain regulates neuroendocrine axes, energy and glucose homeostasis, and several neurological functions. The lateral hypothalamic area (LHA) contains numerous neurons that respond to a systemic GH injection by expressing the phosphorylated STAT5, a GH receptor (GHR) signaling marker. However, the potential role of GHR signaling in the LHA is unknown. In this study, we demonstrated that ∼70% of orexin- and leptin receptor (LepR)-expressing neurons in the LHA are responsive to GH. Male mice carrying inactivation of the Ghr gene in the LHA were generated via bilateral injections of an adeno-associated virus. In ad libitum -fed mice, GHR ablation in LHA neurons did not significantly change energy and glucose homeostasis. Subsequently, mice were subjected to 5 d of 40% food restriction. Food restriction decreased body weight, energy expenditure, and carbohydrate oxidation. These effects were similarly observed in control and LHA ΔGHR mice. While food-deprived control mice progressively increased ambulatory/exploratory activity and food-seeking behavior, LHA ΔGHR mice did not show hyperactivity induced by food restriction. GHR ablation in the LHA reduced the percentage of orexin neurons expressing c-Fos during food restriction. Additionally, an acute GH injection increased the expression of c-Fos in LHA ORX neurons. Inactivation of Ghr in LepR-expressing cells did not prevent hyperactivity in food-deprived mice, whereas whole-brain Ghr knock-out mice showed reduced ambulatory activity during food restriction. Our findings indicate that GHR signaling in the LHA regulates the activity of orexin neurons and is necessary to increase food-seeking behavior in food-deprived male mice., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 the authors.)

In experiments on male Wistar rats, the stages of adaptive changes in the rhythm of periodic electrical activity in the small intestine during food deprivation were identified and the effect of GABA on changes of the rhythm under these conditions was assessed. It was found that on days 1-3 of food deprivation, the migrating myoelectric complex (MMC) in the small intestine is preserved, but the cycle becomes rarer. On days 4-6, MMC disappears, irregular and regular activity with no periods of quiescence is recorded. On days 7-9, predominantly irregular activity of the small intestine with short quiescence periods is observed. Enteral administration of GABA at different stages of food deprivation modulates electrical activity and preserves small intestinal MMC., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)

Feed restriction could induce physiological stress in broiler chickens, leading to welfare issues. Prenatal stimulation could improve stress-coping mechanisms in poultry. The present study aimed to elucidate the effects of subjecting developing embryos to auditory stimulation on physiological stress response to feed restriction in broiler chickens at market age. A total of 423 hatching eggs of Cobb 500 (Gallus domesticus) were subjected to the following auditory treatments: 1) no additional sound treatment other than the background sound of the incubator's compressors at 40 dB (CONTROL), 2) exposure to pre-recorded traffic noise at 90 dB (NOISE), and 3) exposure to Mozart's Sonata for Two Pianos in D Major, K 488 at 90 dB) (MUSIC). The NOISE and MUSIC treatments were for 20 min/h for 24 h (a total of 8 h/d), starting from embryonic days (ED) 12 to hatching. On d 42, an equal number of birds from each prenatal auditory stimulation (PAS) group were subjected to either ad libitum feeding (AL) or 30-h of feed restriction (FR) in a completely randomised design. The FR chickens exhibited significantly higher serum levels of corticosterone (CORT), and heat shock protein (HSP) 70 compared to those of AL. Prenatal auditory stimulation, particularly NOISE, led to lower serum levels of CORT and alpha-1-acid glycoprotein (AGP) levels compared to the CONTROL group. Additionally, NOISE significantly increased brain mRNA glucocorticoid receptor and HSP70 gene expression. The cecal population of E. coli and Lactobacillus spp. was not significantly affected by prenatal auditory stimulation. In conclusion, our findings suggest that prenatal auditory stimulation, particularly NOISE, positively impacts broiler chickens' ability to cope with feed restriction., Competing Interests: DISCLOSURES The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Climate change is increasingly manifesting in temperate regions. Laying hens are highly sensitive to heat stress and mitigation strategies should be implemented to reduce the negative effects. The goal of this experiment was to evaluate the effects of betaine in drinking water (0.55 g/L) and 4 h feed restriction during peak heat stress on laying performance, egg quality, blood gas parameters, body temperature (Tb), and oxidative stress in 2 different breeds of laying hens. Therefore, 448 ISA Brown hens (25 wk) and 448 Lohmann LSL classic laying hens (26 wk) were housed in 128 cages (7 hens/cage). Thermoneutral (TN) data was collected for 21 d before cyclic heat stress (HS) (21d; 32 ± 2°C; 6 h daily). During HS, hens were divided into 4 treatments: 1) feed restriction (FR), 2) betaine supplementation in drinking water (BET), 3) feed restriction and betaine supplementation in drinking water (FR-BET), or 4) control (CON). The effects were evaluated after 1 wk of HS (acute heat stress; AHS) and 3 wk of HS (chronic heat stress; CHS). Laying rate and egg mass (EM) diminished during CHS but decreased more in white than brown hens (2.78% and 1.94%; -1.57% and -0.81%, respectively; P = 0.004) and remained unaltered by BET or FR. During AHS, average daily feed intake (ADFI) increased compared to TN, but the increase was higher in white than brown hens (6.36% and 2.62%, respectively; P = 0.001). Egg shell quality deteriorated during AHS and CHS, but was most affected in white hens, FR or BET did not impact this. Blood pCO 2 , HCO 3 - and base excess significantly decreased during AHS and CHS, but pH and iCa were unaltered. Blood glucose increased in white hens during AHS compared to TN (P < 0.001), while plasma malondialdehyde increased in brown hens (P < 0.001). Results indicated that laying hens experienced HS, but breed differences were observed and white hens were generally most affected. FR affected feed conversion ratio negatively during CHS. However, FR and BET could not improve laying performance, egg quality, Tb, or blood parameters during HS., Competing Interests: DISCLOSURES None of the authors has any financial or personal relationships that could inappropriately influence or bias the content of the paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Food deprivation is used in many experimental models and is becoming increasingly prevalent in human diets. The impact of food deprivation on specific brain regions, including the nucleus of the tractus solitarius (NTS), a region that is involved in hunger and satiety sensing, remains to be determined. The NTS is a heterogeneous nucleus that includes corticotropin releasing factor receptor 1 (CRF1) neurons. CRF1 is implicated in both stress and appetite regulation, but the effects of food deprivation on CRF1 NTS neurons are unclear. We used immunofluorescence to examine the effects of 24-hour food deprivation on NTS activity in male and female Sprague-Dawley (SD) rats and CRF1-cre rats using cFos, an immediate early gene and neuronal marker of activation. NTS activity was increased in food deprived male but not female SD rats. In food deprived CRF1-cre rats, males had an increased proportion of active CRF1 + neurons with no change in females. In CRF1-cre rats, increased global NTS activity was observed in food deprived and refed males. Activation of CRF1 + neurons was also increased after deprivation but was reduced by refeeding. In females, food deprivation decreased global NTS activity that was then increased by refeeding, while CRF1 activity was unchanged. Collectively, these data suggest the NTS is differentially activated after food deprivation in a sex-specific manner, whereby males are more sensitive than females. These results provide insight into the role of brainstem stress circuitry in changes associated with conditions including intermittent fasting and eating disorders like anorexia., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In addition to its sweet taste, glucose has potent and rapid postoral actions (appetition) that enhance its reward value. This has been demonstrated by the experience-induced preference for glucose over initially preferred nonnutritive sweetener solutions in 24-h choice tests. However, some sweetener solutions (e.g., 0.8% sucralose) have inhibitory postoral actions that may exaggerate glucose appetition whereas others (e.g., 0.1% sucralose + 0.1% saccharin, S+S) do not. Experiment 1 revealed that food-restricted (FR) male C57BL/6J mice displayed similar rapid glucose appetition effects (stimulation of glucose licking within minutes) and conditioned flavor preferences following 1-h experience with flavored 0.8% sucralose or 0.1% S+S and 8% glucose solutions. Thus, the inhibitory effects of 0.8% sucralose observed in 24-h tests were not apparent in 1-h tests. Experiment 2 evaluated the effects of food deprivation state and sweetener concentration on glucose appetition in female mice. Unlike FR mice tested with 0.1% S+S and 8% glucose, ad libitum (AL) fed mice displayed no stimulation of 8% glucose licking in the 1-h tests. A second ad libitum group (AL) tested with 0.2% S+S and 16% glucose solutions displayed stimulation of 16% glucose licking by the third 1-h test. Both AL groups, like the FR group, developed a preference for the glucose-paired flavor over the S+S paired flavor. Thus, food restriction promotes increased glucose licking but is not required for a conditioned preference. The FR male mice (Exp. 1) and FR female mice (Exp. 2) showed similar appetition responses (licking stimulation and flavor preference) to 8% glucose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In most species studied, energy deficits inhibit female reproductive behavior, but the location and nature of energy sensors and how they affect behavior are unknown. Progress has been facilitated by using Drosophila melanogaster , a species in which reproduction and food availability are closely linked. Adult males and females were either fed or food deprived (FD) and then tested in an arena with a fed, opposite-sex conspecific with no food in the testing arena. Only FD females (not FD males) significantly decreased their copulation rate and increased their copulation latency, and the effects of FD were prevented in females fed either yeast alone or glucose alone, but not sucralose alone, cholesterol alone, or amino acids alone. It is well-known that high-fat diets inhibit copulation rate in this species, and the effects of FD on copulation rate were mimicked by treatment with an inhibitor of glucose but not free fatty acid oxidation. The availability of oxidizable glucose was a necessary condition for copulation rate in females fed either yeast alone or fed a nutritive fly medium, which suggests that the critical component of yeast for female copulation rate is oxidizable glucose. Thus, female copulation rate in D. melanogaster is sensitive to the availability of oxidizable metabolic fuels, particularly the availability of oxidizable glucose or substrates/byproducts of glycolysis. NEW & NOTEWORTHY Copulation rate was decreased in food-deprived female but not in male adults when tested without food in the testing arena. Copulation rate was 1 ) maintained by feeding glucose alone, yeast alone, nutritive medium lacking yeast, but not sucralose, amino acids, or cholesterol alone; 2 ) decreased by inhibition of glycolysis in females fed either nutritive medium or yeast alone; and 3 ) not affected by inhibition of fatty acid oxidation. Thus, female copulation rate was linked to glycolytic status.

Food restriction can have profound effects on various aspects of behavior, physiology, and morphology. Such effects might be amplified in animals that are highly active, given that physical activity can represent a substantial fraction of the total daily energy budget. More specifically, some effects of food restriction could be associated with intrinsic, genetically based differences in the propensity or ability to perform physical activity. To address this possibility, we studied the effects of food restriction in four replicate lines of High Runner (HR) mice that have been selectively bred for high levels of voluntary wheel running. We hypothesized that HR mice would respond differently than mice from four non-selected Control (C) lines. Healthy adult females from generation 65 were housed individually with wheels and provided access to food and water ad libitum for experimental days 1-19 (Phase 1), which allowed mice to attain a plateau in daily running distances. Ad libitum food intake of each mouse was measured on days 20-22 (Phase 2). After this, each mouse experienced a 20 % food restriction for 7 days (days 24-30; Phase 3), and then a 40 % food restriction for 7 additional days (days 31-37; Phase 4). Mice were weighed on experimental days 1, 8, 9, 15, 20, and 23-37 and wheel-running activity was recorded continuously, in 1-minute bins, during the entire experiment. Repeated-measures ANOVA of daily wheel-running distance during Phases 2-4 indicated that HR mice always ran much more than C, with values being 3.29-fold higher during the ad libitum feeding trial, 3.58-fold higher with -20 % food, and 3.06-fold higher with -40 % food. Seven days of food restriction at -20 % did not significantly reduce wheel-running distance of either HR (-5.8 %, P = 0.0773) or C mice (-13.3 %, P = 0.2122). With 40 % restriction, HR mice showed a further decrease in daily wheel-running distance (P = 0.0797 vs. values at 20 % restriction), whereas C mice did not (P = 0.4068 vs. values at 20 % restriction) and recovered to levels similar to those on ad libitum food (P = 0.3634). For HR mice, daily running distances averaged 11.4 % lower at -40 % food versus baseline values (P = 0.0086), whereas for C mice no statistical difference existed (-4.8 %, P = 0.7004). Repeated-measures ANOVA of body mass during Phases 2-4 indicated a highly significant effect of food restriction (P = 0.0001), but no significant effect of linetype (P = 0.1764) and no interaction (P = 0.8524). Both HR and C mice had a significant reduction in body mass only when food rations were reduced by 40 % relative to ad libitum feeding, and even then the reductions averaged only -0.60 g for HR mice (-2.6 %) and -0.49 g (-2.0 %) for C mice. Overall, our results indicate a surprising insensitivity of body mass to food restriction in both high-activity (HR) and ordinary (C) mice, and also insensitivity of wheel running in the C lines of mice, thus calling for studies of compensatory mechanisms that allow this insensitivity., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

There is a link between metabolism and reproduction as metabolic hormones affect hypothalamus-pituitary-testis (HPT) hormonal functions and vice versa. The aim of the present study was to investigate the effects of negative energy balance on the reproductive system in male goldfish exposed to testosterone (T) and 17β-estradiol (E 2 ). Following 7 days of food deprivation (FD), ANOVA models showed significant FD × sex steroid interactions on sperm quality and circulating sex steroid levels. When FD effects were investigated, 11-ketotestosterone (11-KT) level and sperm motility and velocity decreased in food-deprived goldfish in the control group. In E 2 -exposed goldfish, FD decreased sperm production in addition to sperm motility and velocity that coincided with an elevation of circulating E 2 level. However, FD did not significantly impact sex steroids and sperm quality in T-exposed goldfish. ANOVA models showed non-significant FD × sex steroid interactions for HSI, GSI, circulating luteinizing hormone (Lh) level, and metabolic (preproghrelin, goat and nucb2) and reproductive (kiss1, gpr54 and gnrh3) mRNAs. Furthermore, results showed that FD decreased HSI, and increased Lh levels and testicular preproghrelin and goat mRNAs, while sex steroids increased mid-brain nucb2, kiss1 and gpr54 mRNAs. Together, our results suggest that FD-induced inhibition of androgenesis resulted in diminished sperm quality associated with activation of the testicular ghrelinergic system, and negative feedback of 11-KT increased Lh level. The FD-induced testicular metabolic and hormonal system was impacted in goldfish exposed to sex steroids. However, the negative effects of FD on sperm quality were accelerated in E 2 -exposed goldfish due to estrogenic activity. This study provides novel information to better understand metabolic-associated reproductive disorders in fish., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A multitude of animal species undergo prolonged fasting events at regularly occurring life history stages. During such periods of food deprivation, individuals need to suppress their appetite. The satiety signalling gut hormone ghrelin has received much attention in this context in studies looking at mammalian systems. In wild birds, however, knowledge on the ghrelin system and its role during extended fasts is still scarce. In this study, we collected plasma samples for measurements of circulating ghrelin concentrations from adult southern rockhopper penguins (Eudyptes chrysocome chrysocome) during the three to four week-long moult-fast that they repeat annually to replace their feathers. We further sampled chicks before and after feeding bouts and non-moulting adults. Circulating ghrelin levels did not differ significantly between fed and unfed chicks but chicks had significantly lower plasma ghrelin levels compared to adults. Furthermore, penguins in late moult (i.e. individuals at the end of the prolonged fasting bout) had higher ghrelin levels compared to non-moulting adults. Our results show elevated levels of circulating ghrelin during moult and generally lower levels of ghrelin in chicks than in adults regardless of feeding state. Given the scarcity or absence of knowledge on the function of ghrelin in seabirds and in fasting birds in general, our results add greatly to our understanding of the avian ghrelin system., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Mammals have evolved sex-specific adaptations to reduce energy usage in times of food scarcity. These adaptations are well described for peripheral tissue, though much less is known about how the energy-expensive brain adapts to food restriction, and how such adaptations differ across the sexes. Here, we examined how food restriction impacts energy usage and function in the primary visual cortex (V1) of adult male and female mice. Molecular analysis and RNA sequencing in V1 revealed that in males, but not in females, food restriction significantly modulated canonical, energy-regulating pathways, including pathways associated waith AMP-activated protein kinase, peroxisome proliferator-activated receptor alpha, mammalian target of rapamycin, and oxidative phosphorylation. Moreover, we found that in contrast to males, food restriction in females did not significantly affect V1 ATP usage or visual coding precision (assessed by orientation selectivity). Decreased serum leptin is known to be necessary for triggering energy-saving changes in V1 during food restriction. Consistent with this, we found significantly decreased serum leptin in food-restricted males but no significant change in food-restricted females. Collectively, our findings demonstrate that cortical function and energy usage in female mice are more resilient to food restriction than in males. The neocortex, therefore, contributes to sex-specific, energy-saving adaptations in response to food restriction., Competing Interests: ZP, DK, PM, MR, EO, NR No competing interests declared, (© 2023, Padamsey et al.)

Food deprivation has been associated with the development of metabolic pathologies. Few studies have explored the repercussions of a partial food deprivation following the reestablishment of an ad libitum diet. This study investigates the impact of a partial food deprivation (an 8-hour food intake restriction coupled with a 4-hour feeding window during the active phase) and the subsequent return to ad libitum feeding on the glycemic curve, food intake, and locomotor behavior. Wistar rats aged 45 days were subjected to 6 weeks of a partial food deprivation followed by 6 weeks of ad libitum feeding. Body weight, visceral fat, food intake, circadian glycemia, oral glucose tolerance, and locomotor activity were evaluated. It was found that the partial food deprivation resulted in the reduction of both the body weight and food intake; however, it increased visceral fat by 60%. Circadian glycemic values were altered at all intervals during the light phase, and glucose sensitivity improved at 60 minutes in the oral glucose tolerance test (OGTT). In the food-deprived group, the locomotor activity rhythm was reduced, with an observed delay in the peak of activity, reduction in total activity, and a decrease in the rhythmicity percentage. After the reestablishment of the ad libitum feeding, there was recovery of body weight, no difference in visceral fat, normalization of the food intake pattern, circadian glycemia, and oral glucose tolerance. Additionally, the return to ad libitum feeding restored locomotor activity, although the duration required for its complete recovery warrants further investigation. In conclusion, partial food deprivation induces physio-metabolic changes in rats, most of which are reversed after reestablishing ad libitum feeding.

Growth hormone (GH) receptor (GHR) is abundantly expressed in neurons that co-release the agouti-related protein (AgRP) and neuropeptide Y (NPY) in the arcuate nucleus of the hypothalamus (ARH). Since ARH AgRP/NPY neurons regulate several hypothalamic-pituitary-endocrine axes, this neuronal population possibly modulates GH secretion via a negative feedback loop, particularly during food restriction, when ARH AgRP/NPY neurons are highly active. The present study aims to determine the importance of GHR signaling in ARH AgRP/NPY neurons on the pattern of GH secretion in fed and food-deprived male mice. Additionally, we compared the effect of two distinct situations of food deprivation: 16 h of fasting or four days of food restriction (40% of usual food intake). Overnight fasting strongly suppressed both basal and pulsatile GH secretion. Animals lacking GHR in ARH AgRP/NPY neurons (AgRP ∆GHR mice) did not exhibit differences in GH secretion either in the fed or fasted state, compared to control mice. In contrast, four days of food restriction increased GH pulse frequency, basal GH secretion, and pulse irregularity/complexity (measured by sample entropy), whereas pulsatile GH secretion was not affected in both control and AgRP ∆GHR mice. Hypothalamic Ghrh mRNA levels were unaffected by fasting or food restriction, but Sst expression increased in acutely fasted mice, but decreased after prolonged food restriction in both control and AgRP ∆GHR mice. Our findings indicate that short-term fasting and prolonged food restriction differentially affect the pattern of GH secretion, independently of GHR signaling in ARH AgRP/NPY neurons., (© 2023 British Society for Neuroendocrinology.)

Food-anticipatory nose poking is a unique food-seeking behavior driven by the food-entrainable oscillator. Here, we present a protocol to record a novel food-seeking nose poking behavior in mice under temporally restricted feeding followed by food deprivation using the open-source feeding experimentation device version 3 (FED3). We describe steps for setting up the FED3 and cage, training, and habituation. We then detail procedures for setting up the schedule for time-restricted feeding and food deprivation and for generating ethograms from FED3 data. For complete details on the use and execution of this protocol, please refer to Ehichioya et al. 1 ., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The aim was to evaluate the quality of the sheep skin of different sex classes submitted to different levels of feed restriction. Sheep without defined racial pattern of different sex classes (15 non-castrated males, 15 castrated males and 15 females), with initial body weight of 18.1 ± 0.4 kg and mean age of 90 days were distributed in a factorial 3 × 3, with three sex classes and 3 levels of feed restriction (ad libitum intake and restricted intake at 70 and 80%), with 5 repetitions. After slaughter, the skins were collected for physical-mechanical tests. The effect of the sex classes x levels of dietary restriction interaction was observed for transverse thickness and longitudinal rupture elongation (p < 0.05). Animals fed ad libitum had greater longitudinal transverse thickness (p < 0.05). Animals fed ad libitum and 70% feed restriction showed greater transverse elongation at break (p < 0.05). As for the difference between sex classes in the transverse thickness variable for tearing strength, the interaction sex classes x levels of feed restriction for transverse thickness, longitudinal thickness, transverse tearing strength and longitudinal tearing strength occurred (p < 0.05). Feed restriction reduces the physical quality of the skin of sheep of different sex classes, and the use of castrated male sheep in positive energy balance is recommended to obtain leather with greater thickness, longitudinal rupture elongation and transverse tear strength., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Spontaneous lipolysis results in the breakdown of milk fat by the lipoprotein lipase (EC: 3.1.1.34), an enzyme present in milk. Free fatty acids (FFAs) and by-products released in milk during lipolysis can alter both the organoleptic value of milk (off-flavors release) and technological properties of dairy products (decrease in creaming capabilities). Current climate change is having significant impacts on the feeding of grazing animals, with negative consequences on the availability and quality of grass. We and others have demonstrated that dietary restriction increases milk lipolysis in the cow species. However, no data about the impact of feed restriction on milk lipolysis is available in the ewe species. Thus, this paper aims to investigate the effect of feed restriction on milk characteristics with regard to lipolysis values in dairy ewes. Two groups of 24 multiparous Lacaune ewes in mid-lactation received a "non-restricted" control diet (100% of ad libitum DM intake) or a "restricted" (RESTR) diet (65% of ad libitum DM intake) according to a 2 × 2 crossover design. Milk gross composition together with lipolysis analyses were performed. Blood samples were also screened for metabolites or hormone concentrations. The RESTR treatment induced a decrease in milk production (- 21% compared with control treatment) and a modification of the metabolism of dairy ewes characterized by an increase in plasma non-esterified fatty acids (NEFAs), which represents the balance between adipose tissue mobilization and the use of NEFA by other tissues (+153%), cholesterol (+17%) and β-hydroxybutyrate (+4 %) levels. As a result, a decrease in BW of dairy ewes was observed (-7%). Feed restriction also resulted in a decrease in milk lipolysis estimated by the milk FFA measured by the copper-soap method (-63 and -62%, respectively, for morning and evening milking) or by the reference Bureau of Dairy Industry method (-51 and -57%, respectively, for morning and evening milking). The decrease in milk spontaneous lipolysis under feed restriction was not associated with a decrease in lipoprotein lipase activity in ewes. These results will be completed with proteomic and lipidomic studies in milk samples to better understand mechanisms initiated in the ewe species specifically with regard to lipolysis in milk., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

The growth hormone secretagogue receptor (GHSR), primarily known as the receptor for the hunger hormone ghrelin, potently controls food intake, yet the specific Ghsr-expressing cells mediating the orexigenic effects of this receptor remain incompletely characterized. Since Ghsr is expressed in gamma-aminobutyric acid (GABA)-producing neurons, we sought to investigate whether the selective expression of Ghsr in a subset of GABA neurons is sufficient to mediate GHSR's effects on feeding. First, we crossed mice that express a tamoxifen-dependent Cre recombinase in the subset of GABA neurons that express glutamic acid decarboxylase 2 (Gad2) enzyme (Gad2-CreER mice) with reporter mice, and found that ghrelin mainly targets a subset of Gad2-expressing neurons located in the hypothalamic arcuate nucleus (ARH) and that is predominantly segregated from Agouti-related protein (AgRP)-expressing neurons. Analysis of various single-cell RNA-sequencing datasets further corroborated that the primary subset of cells coexpressing Gad2 and Ghsr in the mouse brain are non-AgRP ARH neurons. Next, we crossed Gad2-CreER mice with reactivable GHSR-deficient mice to generate mice expressing Ghsr only in Gad2-expressing neurons (Gad2-GHSR mice). We found that ghrelin treatment induced the expression of the marker of transcriptional activation c-Fos in the ARH of Gad2-GHSR mice, yet failed to induce food intake. In contrast, food deprivation-induced refeeding was higher in Gad2-GHSR mice than in GHSR-deficient mice and similar to wild-type mice, suggesting that ghrelin-independent roles of GHSR in a subset of GABA neurons is sufficient for eliciting full compensatory hyperphagia in mice., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Background: In this study, we investigated the effects of swimming activity and feed restriction on digestion and antioxidant enzyme activities in juvenile rainbow trout (average body weight of 26.54 ± 0.36 g)., Methods: The stomach, liver and kidney tissues were obtained from four distinct groups: the static water group (fish were kept in static water and fed to satiation), the feeding restricted group (fish were kept in static water with a 25% feed restriction), the swimming exercised group (fish were forced to swimming at a flow rate of 1 Body Length per second (BL/s)) and the swimming exercised-feed restricted group (subjected to swimming exercise at a 1 BL/s flow rate along with a 25% feed restriction). We determined the levels of glutathione, lipid peroxidation and the activities of catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase and lactate dehydrogenase, as well as the presence of reactive oxygen species in the tissues obtained from the fish. Additionally, the activities of pepsin, protease, lipase and arginase in these tissues were measured., Results: Swimming activity and feed restriction showed different effects on the enzyme activities of the fish in the experimental groups., Conclusion: It can be concluded that proper nutrition and exercise positively influence the antioxidant system and enzyme activities in fish, reducing the formation of free radicals. This situation is likely to contribute to the fish's development., (© 2024 The Authors. Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

Compensatory growth (CG) is a physiological response that accelerates growth following a period of nutrient limitation, with the potential to improve growth efficiency and meat quality in cattle. However, the underlying molecular mechanisms remain poorly understood. In this study, 60 Huaxi cattle were divided into one ad libitum feeding (ALF) group and two restricted feeding groups (75% restricted, RF75; 50% restricted, RF50) undergoing a short-term restriction period followed by evaluation of CG. Detailed comparisons of growth performance during the experimental period, as well as carcass and meat quality traits, were conducted, complemented by a comprehensive transcriptome analysis of the longissimus dorsi muscle using differential expression analysis, gene set enrichment analysis (GSEA), gene set variation analysis (GSVA), and weighted correlation network analysis (WGCNA). The results showed that irrespective of the restriction degree, the restricted animals exhibited CG, achieving final body weights comparable to the ALF group. Compensating animals showed differences in meat quality traits, such as pH, cooking loss, and fat content, compared to the ALF group. Transcriptomic analysis revealed 57 genes and 31 pathways differentially regulated during CG, covering immune response, acid-lipid metabolism, and protein synthesis. Notably, complement-coagulation-fibrinolytic system synergy was identified as potentially responsible for meat quality optimization in RF75. This study provides novel and valuable genetic insights into the regulatory mechanisms of CG in beef cattle.

Growth hormone (Gh) regulates growth in part by stimulating the liver to synthesize and release insulin-like growth factor-1 (Igf1), which then promotes somatic growth. However, for fish experiencing food limitation, elevated blood Gh can occur even with low circulating Igf1 and slow growth, suggesting that nutritional stress can alter the sensitivity of liver Igf1 synthesis pathways to Gh. Here, we examined how recent feeding experience affected Gh regulation of liver Igf1 synthesis pathways in juvenile gopher rockfish (Sebastes carnatus) to illuminate mechanisms underlying the nutritional modulation of Igf1 production. Juvenile gopher rockfish were maintained under conditions of feeding or complete food deprivation (fasting) for 14 d and then treated with recombinant sea bream (Sparus aurata) Gh or saline control. Gh upregulated hepatic igf1 mRNA levels in fed fish but not in fasted fish. The liver of fasted rockfish also showed a lower relative abundance of gene transcripts encoding teleost Gh receptors 1 (ghr1) and 2 (ghr2), as well as reduced protein levels of phosphorylated janus tyrosine kinase 2 (pJak2) and signal transducer and activator of transcription 5 (pStat5), which function to induce igf1 gene transcription following Gh binding to Gh receptors. Relative hepatic mRNA levels for suppressors of cytokine signaling (Socs) genes socs2, socs3a, and socs3b were also lower in fasted rockfish. Socs2 can suppress Gh activation of Jak2/Stat5, and fasting-related variation in socs expression may reflect modulated inhibitory control of igf1 gene transcription. Fasted rockfish also had elevated liver mRNA abundances for lipolytic hormone-sensitive lipase 1 (hsl1) and Igf binding proteins igfbp1a, -1b and -3a, reduced liver mRNAs encoding igfbp2b and an Igfbp acid labile subunit-like (igfals) gene, and higher transcript abundances for Igf1 receptors igf1ra and igf1rb in skeletal muscle. Together, these findings suggest that food deprivation impacts liver Igf1 responsiveness to Gh via multiple mechanisms that include a downregulation of hepatic Gh receptors, modulation of the intracellular Jak2/Stat5 transduction pathway, and possible shifts in Socs-inhibitory control of igf1 gene transcription, while also demonstrating that these changes occur in concert with shifts in liver Igfbp expression and muscle Gh/Igf1 signaling pathway components., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

To examine the effects of decreased food consumption on toxicological parameters in juvenile rats, rats on postnatal day 21 were fed 40%, 50% (only four weeks), and 60% less food, compared to that of controls for four or eight weeks, and clinical observations, measurement of body and organ weights, morphological differentiation analysis, clinical pathology, and macroscopic and microscopic examinations were conducted. The body weight decreased depending on the degree of food restriction (FR). Cleavage of the balano-preputial skinfold was delayed, and cell debris in the epididymal lumen was noted as a related finding after four-week FR. Vaginal opening was also delayed, and some histopathological findings, such as absence of corpus luteum in the ovary, mucinous degeneration in the vagina, and immature uterus, were noted after eight-week FR. Erythrocyte count increased after four-week FR, but slightly decreased in males only after eight-week FR, and decreased leukocyte and/or reticulocyte counts, accompanied by related histopathological findings were noted after four- and eight-week FR. In blood chemistry, the levels of total protein including globulin, glucose, triglyceride, and calcium decreased, and sodium and chloride increased after four- and eight-week FR. Increases in activities of aspartate transaminase and lactate dehydrogenase and total bilirubin levels were noted after four-week FR, which were attenuated after eight-week FR. The effects of FR seemed to be more remarkable after four weeks. In drug safety evaluation, findings caused by malnutrition should be considered in juvenile toxicity studies when decreased food consumption is observed.

In the pond snail Lymnaea stagnalis , serotonin (5-HT) plays an important role in feeding behavior and its associated learning (e.g., conditioned taste aversion: CTA). The 5-HT content in the central nervous system (CNS) fluctuates with changes in the nutritional status, but it is also expected to be influenced by changes in the serotonin transporter (SERT) expression level. In the present study, we identified SERT in Lymnaea and observed its localization in 5-HTergic neurons, including the cerebral giant cells (CGCs) in the cerebral ganglia and the pedal A cluster neurons and right and left pedal dorsal 1 neurons in the pedal ganglia by in situ hybridization. Real-time PCR revealed that the SERT mRNA expression level was lower under severe food deprivation than under mild food deprivation in the whole CNS as well as in a single CGC. These results inversely correlated with previous data that the 5-HT content in the CNS was higher in the severely food-deprived state than in the mildly food-deprived state. Furthermore, in single CGCs, we observed that the 5-HT level was significantly increased in the severely food-deprived state compared with the mildly food-deprived state. Our present findings suggest that changes in the SERT expression level associated with food deprivation may affect 5-HT signaling, probably contributing to learning and memory mechanisms in Lymnaea .

Nutritional status plays an important role in cognitive functioning, but there is disagreement on the role that food deprivation plays in learning and memory. In this study, we investigated the behavioral and transcriptional effects induced by different lengths of food deprivation: 1 day, which is a short time period of food deprivation, and 3 days, which is an 'intermediate' level of food deprivation. Snails were subjected to different feeding regimens and then trained for operant conditioning of aerial respiration, where they received a single 0.5 h training session followed by a long-term memory (LTM) test 24 h later. Immediately after the memory test, snails were killed and the expression levels of key genes for neuroplasticity, energy balance and stress response were measured in the central ring ganglia. We found that 1 day of food deprivation was not sufficient to enhance snails' LTM formation and subsequently did not result in any significant transcriptional effects. However, 3 days of food deprivation resulted in enhanced LTM formation and caused the upregulation of neuroplasticity and stress-related genes and the downregulation of serotonin-related genes. These data provide further insight into how nutritional status and related molecular mechanisms impact cognitive function., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2023. Published by The Company of Biologists Ltd.)

Nutritional status affects cognitive function in many types of organisms. In the pond snail Lymnaea stagnalis , 1 day of food deprivation enhances taste aversion learning ability by decreasing the serotonin (5-hydroxytryptamin; 5-HT) content in the central nervous system (CNS). On the other hand, after 5 days of food deprivation, learning ability and the CNS 5-HT concentration return to basal levels. How food deprivation leads to alterations of 5-HT levels in the CNS, however, is unknown. Here, we measured the concentration of the 5-HT precursor tryptophan in the hemolymph and CNS, and demonstrated that the CNS tryptophan concentration was higher in 5-day food-deprived snails than in non-food-deprived or 1-day food-deprived snails, whereas the hemolymph tryptophan concentration was not affected by the duration of food deprivation. This finding suggests the existence of a mediator of the CNS tryptophan concentration independent of food deprivation. To identify the mediator, we investigated autophagic flux in the CNS under different food deprivation conditions. We found that autophagic flux was significantly upregulated by inhibition of the tropomyosin receptor kinase (Trk)-Akt-mechanistic target of rapamycin complex 1 (MTORC1) pathway in the CNS of 5-day food-deprived snails. Moreover, when autophagy was inhibited, the CNS 5-HT content was significantly downregulated in 5-day food-deprived snails. Our results suggest that the hemolymph tryptophan concentration and autophagic flux in the CNS cooperatively regulate learning ability affected by different durations of food deprivation. This mechanism may underlie the selection of behaviors appropriate for animal survival depending on the degree of nutrition.

For many animal species, knowing when to look for food may be as important as knowing where to look. Rats and other species use a feeding-responsive circadian timing mechanism to anticipate, behaviorally and physiologically, a predictable daily feeding opportunity. How this mechanism for anticipating a daily meal accommodates more than one predictable mealtime is unclear. Rats were trained to press a lever for food, and then limited to one or more daily meals at fixed or systematically varying times of day. The rats were able to anticipate up to 4 of 4 daily meals at fixed times of day and two 'daily' meals recurring at 24 h and 26 h intervals. When deprived of food, in constant dark, lever pressing recurred for multiple cycles at expected mealtimes, consistent with the periodicity of the prior feeding schedule. Anticipation did not require the suprachiasmatic nucleus circadian pacemaker. The anticipation rhythms could be simulated using a Kuramoto model in which clusters of coupled oscillators entrain to specific mealtimes based on initial phase and intrinsic circadian periodicity. A flexibly coupled system of food-entrainable circadian oscillators endows rats with adaptive plasticity in daily programming of foraging activity., (© 2022. The Author(s).)

Although prolonged food deprivation is known to cause memory deficits, the underlying mechanisms are only partially understood. In this study, we began to investigate the cellular substrates of food deprivation-induced memory impairments in the invertebrate Aplysia. Following a single trial of noxious stimuli, Aplysia concurrently express short-term sensitization (an elementary form of learning in which withdrawal reflexes are enhanced) and short-term feeding suppression for at least 15 min. Cellular correlates of sensitization and feeding suppression include increased excitability of the tail sensory neurons (TSNs) controlling the withdrawal reflexes, and decreased excitability of feeding decision-making neuron B51, respectively. Recently, 14 days of food deprivation (14DFD) was reported to break the co-expression of sensitization and feeding suppression in Aplysia without health deterioration. Specifically, under 14DFD, sensitization was completely prevented while feeding suppression was present albeit attenuated. This study explored the cellular mechanisms underlying the absent sensitization and reduced feeding suppression under 14DFD. A reduced preparation was used to evaluate the short-term cellular modifications induced by delivering an aversive training protocol in vitro. TSN excitability failed to increase following in vitro training under 14DFD, suggesting that the lack of sensitization may be a consequence of the fact that TSN excitability failed to increase. B51 excitability also failed to decrease following in vitro training, indicating that additional neurons may contribute to the conserved albeit reduced feeding suppression in 14DFD animals. This study lays the foundations for the future use of the Aplysia model system to investigate the mechanisms underlying the memory impairments induced by prolonged food deprivation., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: Prenatal development is reliant on a functioning placenta, which can be influenced by maternal nutrition. Moreover, the variation in cotyledonary capacity within an animal has not been fully examined to date. Therefore, the purpose of this study was to determine the effect of (1) placentome size and (2) maternal nutrient restriction on molecular, microscopic, and macroscopic features of bovine placentomes during late gestation., Methods: Pregnant cows (n = 6) were placed into one of 2 treatments: CON (100% NRC) vs RES (60% of NRC) from day 140 until slaughter at day 240 of gestation. Placentomes of various sizes were perfused to assess macroscopic blood vessel density of the cotyledon. Microscopic imaging and RNA extraction for sequencing was performed., Results: Macroscopic blood vessel density relative to placentome weight was not different (P = 0.42) among small, medium, or large placentomes. Cotyledonary microscopic blood vessel number, area, and perimeter was increased (P < 0.005) in high versus low blood perfusion areas. Differential expressed gene (DEG) analysis showed 209 upregulations and 168 downregulations in the RES group (P ≤ 0.0001). Gene Ontology (GO) analysis showed that downregulated enriched terms were involved in blood vessel and mesenchymal stem cells development, whereas upregulated enriched terms were involved with translation and ribosomal function., Discussion: This study demonstrates that placentome function is uniform across various placentome sizes within an animal. However, microscopic heterogeneity exists within each placentome. Maternal nutrient constraints alter placental transcriptomics which may yield compensatory mechanisms involved in nutrient transport including increased perimeter., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Salamanders are unique among tetrapods in their ability to regenerate their limbs throughout life. Like other poikilothermic amphibians, salamanders also show a remarkable capacity to survive long periods of starvation. Whether the physiological reserves necessary for tissue regeneration are preserved or sacrificed in starved salamanders is unknown. In the current study, we maintained Iberian ribbed newts ( Pleurodeles waltl ) under extreme physiological stress to assess the extent of regeneration and identify the molecular and cellular changes that may occur under such conditions. After 19 months of complete food deprivation, the animals exhibited extensive morphological and physiological adaptations but remained behaviorally active and vigilant. Autophagy was elevated in different tissues and the transformed gut microbiota indicated remodeling of the intestinal tract related to autophagy. Upon limb amputation in animals starved for 21 months, regeneration proceeded with progenitor cell proliferation and migration, leading to limb blastema formation. However, limb outgrowth and patterning were substantially attenuated. Blockage of autophagy inhibited cell proliferation and blastema formation in starved animals, but not in fed animals. Hence, tissue autophagy and the regenerative response were tightly coupled only when animals were under stress. Our results demonstrate that under adverse conditions, salamanders can exploit alternative strategies to secure blastema formation for limb regeneration.

Dopamine-mediated reinforcement and behavioral adaptation is essential to survival. Here, we test the effects of food restriction on dopamine-mediated learning and reinforcement using optical intracranial self-stimulation (oICSS), an optogenetic version of conventional electrical ICSS (also known as brain stimulation reward, BSR). Using mouse genetic lines to express channelrhodopsin selectively in midbrain dopamine neurons, we demonstrate that genetically expressed channelrhodopsin can mediate optically evoked dopamine release and support self-stimulation in a lever-pressing paradigm. Using this midbrain dopamine oICSS preparation, we compare acquisition and rate of pressing in ad libitum versus food restricted mice. Food restriction facilitated both more rapid acquisition of self-stimulation behavior and higher rates of responding; reversing food status after acquisition modulated response vigor in already established behavior. These data suggest that food restriction enhances both the acquisition and expression of dopamine-reinforced self-stimulation responding. These data demonstrate the utility of oICSS for examining changes in reinforcement learning concomitant to neuroadaptations induced in dopamine signaling by experimental manipulations such as food restriction., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Digging behavior is often used to test motor function and repetitive behaviors in mice. Different digging paradigms have been developed for behaviors related to anxiety and compulsion in mouse lines generated to recapitulate genetic mutations leading to psychiatric and neurological disorders. However, the interpretation of these tests has been confounded by the difficulty of determining the motivation behind digging in mice. Digging is a naturalistic mouse behavior that can be focused toward different goals, that is foraging for food, burrowing for shelter, burying objects, or even for recreation as has been shown for dogs, ferrets, and human children. However, the interpretation of results from current testing protocols assumes the motivation behind the behavior often concluding that increased digging is a repetitive or compulsive behavior. We asked whether providing a choice between different types of digging activities would increase sensitivity to assess digging motivation. Here, we present a test to distinguish between burrowing and exploratory digging in mice. We found that mice prefer burrowing when the option is available. When food restriction was used to promote a switch from burrowing to exploration, males readily switched from burrowing to digging outside, while females did not. In addition, when we tested a model of intellectual disability and autism spectrum disorder that had shown inconsistent results in the marble burying test, the Cc2d1a conditional knockout mouse, we found greatly reduced burrowing only in males. Our findings indicate that digging is a nuanced motivated behavior and suggest that male and female rodents may perform it differently., (© 2021 Wiley Periodicals LLC.)

Food restriction promotes drug self-administration; however, the effects of food restriction on the conditioned reinforcing properties of drug-associated stimuli are less clear. We tested the extent to which food restriction modified the conditioned reinforcing properties of a remifentanil-associated stimulus following conditioning with 3.2 or 1.0 μg/kg/infusion of remifentanil. First, we provided restricted (20 g/day standard chow) or ad libitum access to standard chow to rats. Second, within each feeding condition, we exposed rats to 20 intravenous infusions of remifentanil and 20 stimulus presentations that were delivered response independently each day for 5 days. For the experimental group (paired Pavlovian), the remifentanil infusions and stimulus presentations were delivered concurrently. The control group (random control) received the same number of infusions and stimulus presentations, but were not paired. For 28 sessions, we tested the extent to which the stimulus functioned as a conditioned reinforcer by allowing rats to freely respond for presentations of the remifentanil-associated stimulus. Following conditioning with 3.2 μg/kg/infusion of remifentanil, we found that rats that in the Paired Pavlovian group responded for the remifentanil-associated stimulus significantly more than rats in the Random control group, regardless of feeding condition. Following conditioning with 1.0 μg/kg/infusion of remifentanil, the remifentanil-associated stimulus was not associated with conditioned reinforcing properties, regardless of feeding condition. These findings confirm previous research demonstrating that a remifentanil-associated stimulus takes on conditioned reinforcing properties in a dose-dependent manner., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Elephant seals experience natural periods of prolonged food deprivation while breeding, molting, and undergoing postnatal development. Prolonged food deprivation in elephant seals increases circulating glucocorticoids without inducing muscle atrophy, but the cellular mechanisms that allow elephant seals to cope with such conditions remain elusive. We generated a cellular model and conducted transcriptomic, metabolic, and morphological analyses to study how seal cells adapt to sustained glucocorticoid exposure. Seal muscle progenitor cells differentiate into contractile myotubes with a distinctive morphology, gene expression profile, and metabolic phenotype. Exposure to dexamethasone at three ascending concentrations for 48 h modulated the expression of six clusters of genes related to structural constituents of muscle and pathways associated with energy metabolism and cell survival. Knockdown of the glucocorticoid receptor (GR) and downstream expression analyses corroborated that GR mediates the observed effects. Dexamethasone also decreased cellular respiration, shifted the metabolic phenotype toward glycolysis, and induced mitochondrial fission and dissociation of mitochondria-endoplasmic reticulum (ER) interactions without decreasing cell viability. Knockdown of DNA damage-inducible transcript 4 (DDIT4), a GR target involved in the dissociation of mitochondria-ER membranes, recovered respiration and modulated antioxidant gene expression in myotubes treated with dexamethasone. These results show that adaptation to sustained glucocorticoid exposure in elephant seal myotubes involves a metabolic shift toward glycolysis, which is supported by alterations in mitochondrial morphology and a reduction in mitochondria-ER interactions, resulting in decreased respiration without compromising cell survival.

Lowered glucose availability, sensed by the hindbrain, has been suggested to enhance gluconeogenesis and food intake as well as suppress reproductive function. In fact, our previous histological and in vitro studies suggest that hindbrain ependymal cells function as a glucose sensor. The present study aimed to clarify the hindbrain glucose sensor-hypothalamic neural pathway activated in response to hindbrain glucoprivation to mediate counterregulatory physiological responses. Administration of 2-deoxy-D-glucose (2DG), an inhibitor of glucose utilization, into the fourth ventricle (4V) of male rats for 0.5 hour induced messenger RNA (mRNA) expression of c-fos, a marker for cellular activation, in ependymal cells in the 4V, but not in the lateral ventricle, the third ventricle or the central canal without a significant change in blood glucose and testosterone levels. Administration of 2DG into the 4V for 1 hour significantly increased blood glucose levels, food intake, and decreased blood testosterone levels. Simultaneously, the expression of c-Fos protein was detected in the 4V ependymal cells; dopamine β-hydroxylase-immunoreactive cells in the C1, C2, and A6 regions; neuropeptide Y (NPY) mRNA-positive cells in the C2; corticotropin-releasing hormone (CRH) mRNA-positive cells in the hypothalamic paraventricular nucleus (PVN); and NPY mRNA-positive cells in the arcuate nucleus (ARC). Taken together, these results suggest that lowered glucose availability, sensed by 4V ependymal cells, activates hindbrain catecholaminergic and/or NPY neurons followed by CRH neurons in the PVN and NPY neurons in the ARC, thereby leading to counterregulatory responses, such as an enhancement of gluconeogenesis, increased food intake, and suppression of sex steroid secretion., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Growing evidence suggests that internal factors influence how we perceive the world. However, it remains unclear whether and how motivational states, such as hunger and satiety, regulate perceptual decision-making in the olfactory domain. Here, we developed a novel behavioral task involving mixtures of food and nonfood odors (i.e., cinnamon bun and cedar; pizza and pine) to assess olfactory perceptual decision-making in humans. Participants completed the task before and after eating a meal that matched one of the food odors, allowing us to compare perception of meal-matched and non-matched odors across fasted and sated states. We found that participants were less likely to perceive meal-matched, but not non-matched, odors as food dominant in the sated state. Moreover, functional magnetic resonance imaging (fMRI) data revealed neural changes that paralleled these behavioral effects. Namely, odor-evoked fMRI responses in olfactory/limbic brain regions were altered after the meal, such that neural patterns for meal-matched odor pairs were less discriminable and less food-like than their non-matched counterparts. Our findings demonstrate that olfactory perceptual decision-making is biased by motivational state in an odor-specific manner and highlight a potential brain mechanism underlying this adaptive behavior., Competing Interests: The authors have declared that no competing interests exist.

BACKGROUNDRoux-en-Y gastric bypass (RYGB) decreases energy intake and is, therefore, an effective treatment of obesity. The behavioral bases of the decreased calorie intake remain to be elucidated. We applied the methodology of microstructural analysis of meal intake to establish the behavioral features of ingestion in an effort to discern the various controls of feeding as a function of RYGB.METHODSThe ingestive microstructure of a standardized liquid meal in a cohort of 11 RYGB patients, in 10 patients with obesity, and in 10 healthy-weight adults was prospectively assessed from baseline to 1 year with a custom-designed drinkometer. Statistics were performed on log-transformed ratios of change from baseline so that each participant served as their own control, and proportional increases and decreases were numerically symmetrical. Data-driven (3 seconds) and additional burst pause criteria (1 and 5 seconds) were used.RESULTSAt baseline, the mean meal size (909.2 versus 557.6 kCal), burst size (28.8 versus 17.6 mL), and meal duration (433 versus 381 seconds) differed between RYGB patients and healthy-weight controls, whereas suck volume (5.2 versus 4.6 mL) and number of bursts (19.7 versus 20.1) were comparable. At 1 year, the ingestive differences between the RYGB and healthy-weight groups disappeared due to significantly decreased burst size (P = 0.008) and meal duration (P = 0.034) after RYGB. The first-minute intake also decreased after RYGB (P = 0.022).CONCLUSIONRYGB induced dynamic changes in ingestive behavior over the first postoperative year. While the eating pattern of controls remained stable, RYGB patients reduced their meal size by decreasing burst size and meal duration, suggesting that increased postingestive sensibility may mediate postbariatric ingestive behavior.TRIAL REGISTRATIONNCT03747445; https://clinicaltrials.gov/ct2/show/NCT03747445.FUNDINGThis work was supported by the University of Zurich, the Swiss National Fund (32003B&#95;182309), and the Olga Mayenfisch Foundation. Bálint File was supported by the Hungarian Brain Research Program Grant (grant no. 2017-1.2.1-NKP-2017-00002).

The black carp (Mylopharyngodon piceus) is an important carnivorous freshwater-cultured species. To understand the molecular basis underlying the response of black carp to fasting, we used RNA-Seq to analyze the liver and brain transcriptome of fasting fish. Annotation to the NCBI database identified 66,609 unigenes, of which 22,841 were classified into the Gene Ontology database and 15,925 were identified in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Comparative analysis of the expression profile between fasting and normal feeding fish revealed 13,737 differentially expressed genes (P < 0.05), of which 12,480 were found in liver tissue and 1257 were found in brain tissue. The KEGG pathway analysis showed significant differences in expression of genes involved in metabolic and immune pathways, such as the insulin signaling pathway, PI3K-Akt signaling pathway, cAMP signaling pathway, FoxO signaling pathway, AMPK signaling pathway, endocytosis, and apoptosis. Quantitative real-time PCR analysis confirmed that expression of the genes encoding the factors involved in those pathways differed between fasting and feeding fish. These results provide valuable information about the molecular response mechanism of black carp under fasting conditions., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The ability to escape predation modulates predator-prey interactions and represents a crucial aspect of organismal life history, influencing feeding, mating success, and survival. Thanatosis, also known as death feigning or tonic immobility (TI), is taxonomically widespread, but understudied in blood-feeding vectors. Hematophagous arthropods, such as ticks, are unique among animals as their predators (birds, mice, lizards, frogs, and other invertebrates) may also be their source of food. Therefore, the trade-off between predator avoidance and host-seeking may shift as the time since the last bloodmeal increases. Because ticks are slow-moving and unable to fly, or otherwise escape, we predicted that they may use TI to avoid predation, but that TI would be influenced by time since the last bloodmeal (starvation). We therefore aimed to quantify this relationship, examining the effect of starvation, body mass, and ontogeny on TI for two tick species: Dermacentor variabilis (Say) (Acari: Ixodidae) and Rhipicephalus sanguineus (Latreille) (Acari: Ixodidae). As we predicted, the duration and use of TI decreased with time since feeding and emergence across species and life stages. Therefore, ticks may become more aggressive in their search for a bloodmeal as they continue to starve, opting to treat potential predators as hosts, rather than avoiding predation by feigning death. Antipredator behaviors such as TI may influence the intensity and amount of time ticks spend searching for hosts, driving patterns of tick-borne pathogen transmission. This identification and quantification of a novel antipredation strategy add a new component to our understanding of tick life history., (© The Author(s) 2021. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The objective of this study was to investigate the effects of feed restriction on mammary miRNAs and coding gene expression in midlactation cows. Five Holstein cows and 6 Montbéliarde cows underwent 6 days of feed restriction, during which feed allowance was reduced to meet 50% of their net energy for lactation requirements. Mammary biopsies were performed before and at the end of the restriction period. Mammary miRNA and mRNA analyses were performed using high-throughput sequencing and microarray analyses, respectively. Feed restriction induced a negative energy balance and decreased milk production and fat and protein yields in both breeds. Feed restriction modified the expression of 27 miRNAs and 374 mRNAs in mammary glands from Holstein cows, whereas no significant miRNA change was observed in Montbéliarde cows. Among the 27 differentially expressed miRNAs, 8 miRNAs were associated with dairy QTL. Analysis of target genes indicate that the 8 most abundantly expressed miRNAs control transcripts related to lipid metabolism, mammary remodeling and stress response. A comparison between the mRNAs targeted by the 8 most strongly expressed miRNAs and 374 differentially expressed mRNAs identified 59 mRNAs in common. The bioinformatic analyses of these 59 mRNAs revealed their implication in lipid metabolism and endothelial cell proliferation. These effects of feed restriction on mammary miRNAs and mRNAs observed in Holstein cows suggest a potential role of miRNAs in mammary structure and lipid biosynthesis that could explain changes in milk production and composition., Competing Interests: NO authors have competing interests.

The behaviour of Dictyostelium discoideum depends on nutrients 1 . When sufficient food is present these amoebae exist in a unicellular state, but upon starvation they aggregate into a multicellular organism 2,3 . This biology makes D. discoideum an ideal model for investigating how fundamental metabolism commands cell differentiation and function. Here we show that reactive oxygen species-generated as a consequence of nutrient limitation-lead to the sequestration of cysteine in the antioxidant glutathione. This sequestration limits the use of the sulfur atom of cysteine in processes that contribute to mitochondrial metabolism and cellular proliferation, such as protein translation and the activity of enzymes that contain an iron-sulfur cluster. The regulated sequestration of sulfur maintains D. discoideum in a nonproliferating state that paves the way for multicellular development. This mechanism of signalling through reactive oxygen species highlights oxygen and sulfur as simple signalling molecules that dictate cell fate in an early eukaryote, with implications for responses to nutrient fluctuations in multicellular eukaryotes.

Food restriction is a robust nongenic, nonsurgical and nonpharmacologic intervention known to improve health and extend lifespan in various species. Food is considered the most essential and frequently consumed natural reward, and current observations have demonstrated homeostatic responses and neuroadaptations to sustained intermittent or chronic deprivation. Results obtained to date indicate that food deprivation affects glutamatergic synapses, favoring the insertion of GluA2-lacking α-Ammino-3-idrossi-5-Metil-4-idrossazol-Propionic Acid receptors (AMPARs) in postsynaptic membranes. Despite an increasing number of studies pointing towards specific changes in response to dietary restrictions in brain regions, such as the nucleus accumbens and hippocampus, none have investigated the long-term effects of such practice in the dorsal striatum. This basal ganglia nucleus is involved in habit formation and in eating behavior, especially that based on dopaminergic control of motivation for food in both humans and animals. Here, we explored whether we could retrieve long-term signs of changes in AMPARs subunit composition in dorsal striatal neurons of mice acutely deprived for 12 hours/day for two consecutive days by analyzing glutamatergic neurotransmission and the principal forms of dopamine and glutamate-dependent synaptic plasticity. Overall, our data show that a moderate food deprivation in experimental animals is a salient event mirrored by a series of neuroadaptations and suggest that dietary restriction may be determinant in shaping striatal synaptic plasticity in the physiological state.

The extent to which reduced insulin secretion during prolonged fasting reflects failure to compensate for whole body insulin resistance or a normal adjustment to potentially increased hepatic insulin action is unknown. We examined the effects of 36- versus 12-h fasting on insulin secretion and whole body versus hepatic insulin action in 13 healthy young males. Hepatic glucose production and insulin action were studied using stable isotopes, whereas whole body insulin action and insulin secretion were studied using an intravenous glucose tolerance test (IVGTT) and minimal modeling. Insulin, glucose, and lipid profiles were subsequently measured during a refeeding meal test. Prolonged fasting caused a minor reduction of first-phase insulin secretion in a context of improved hepatic insulin action, contrasting an increase in whole body insulin resistance. Accordingly, prolonged fasting was associated with opposite-directed effects on hepatic versus whole body insulin secretion disposition indices. Thirty-six-hour fasting compared with 12-h fasting was associated with increased serum insulin levels during the refeeding meal test. In conclusion, reduced insulin secretion during prolonged fasting may represent a healthy response to improved hepatic insulin action. Use of insulin secretion disposition indices without taking organ-specific insulin action into account may lead to erroneous conclusions. NEW & NOTEWORTHY Thirty-six-hour prolonged, compared with 12-h overnight fasting, is associated with slightly reduced first-phase insulin secretion in the face of opposite-directed changes in hepatic versus whole body insulin action in healthy young males. The paradoxical finding of increased hepatic versus decreased whole body insulin secretion disposition indices during prolonged fasting challenges the physiological understanding and validity of insulin secretion disposition indices not taking organ-specific insulin action into account.

In nature, animals often face periods without food caused by seasonal fluctuations and/or prey scarcity. An organism's physiological response to imposed energetic limitations is followed by changes in mitochondrial functioning (adjustment of energy metabolism) and a reduction of non-essential processes. However, this energy-saving strategy can have its costs. In this study, we examined oxidative stress as one of the possible physiological costs of short-term, two-week-long food deprivation on developing amphibian larvae of the crested newts Triturus macedonicus and Triturus ivanbureschi and their hybrids. We investigated whether this exogenous factor additionally affected the oxidative status (fitness-related trait) of hybrid individuals. The fasting treatment led to lower growth and a lower body mass and body condition index of individuals. The results revealed that the antioxidant system (AOS) of food-deprived larvae could not cope in a proper manner with reactive oxygen species production under limited energy availability, leading to higher lipid oxidative damage. The lowest AOS response was observed for H 2 O 2 scavenging parameters (catalase, glutathione peroxidase, and total glutathione), which together with the elevated activity of superoxide dismutase suggested increased H 2 O 2 concentrations. Comparison between parental species and their hybrids showed that hybrid individuals suffered greater oxidative damage (as demonstrated by higher concentrations of lipid peroxides), indicating that they were more susceptible to fasting-induced oxidative stress. Overall, this study illustrates that: (i) an oxidative event is one of the costs amphibian larvae face during short-term periods of fasting, (ii) hybrids are less capable of dealing with this stressful condition, which can lower their chances of survival in a changing environment., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Low energy availability in female athletes often causes hypothalamic amenorrhea and osteoporosis, in turn promoting stress fractures. Mechanisms underlying these conditions remain unclear. Here we show that model mice subjected to food restriction (FR) or FR-plus-voluntary running exercise exhibit significantly reduced bone mineral density, cortical bone parameters and uterine weight than do control mice, and that these parameters worsen in the FR-plus-exercise group. Relative to controls, FR and FR-plus-exercise groups showed significantly lower mineral apposition rate and osteoclast number and significantly reduced serum insulin-like growth factor-1 (IGF1) levels. Outcomes were rescued by ED71 or 1.25(OH) 2 D 3 treatment. Thus, we conclude that administration of active vitamin D analogues represents a possible treatment to prevent these conditions., Competing Interests: Declaration of competing interest All authors state that they have no conflicts of interest with the contents of this article., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Insects, due to their small size, have limited energy storage space, but they also have high metabolic rate, so their hemolymph sugars are incredibly dynamic and play a number of important physiological functional roles in maintaining energetic homeostasis. In contrast to vertebrates, trehalose is generally the primary sugar found in insect hemolymph, which is followed by glucose and fructose. Many analytical chemistry methods exist to measure sugars, yet a direct comparison of methods that can measure all three simultaneously, and trehalose in particular, from low sample volumes, are sparse. Using the honey bee as a model, we directly compare the leading current methods of using High Performance Liquid Chromatography (HPLC) with an evaporative light-scattering detector and Gas Chromatography coupled with Mass Spectrometry (GC-MS) to determine which method would be better for measuring trehalose, glucose, and fructose in terms of reproducibility, accuracy, and sensitivity. Furthermore, we injected the enzyme inhibitors trehalozin (a trehalase inhibitor) and sorbose (a trehalase p-synthase inhibitor) to manipulate the trehalose levels in honey bee foragers as a proof of concept that this sugar can be altered independently of hemolymph glucose and fructose levels. Overall the HPLC method was less reproducible for measuring fructose and glucose, and it also had lower sensitivity for measuring trehalose. Consequently, significant differences in trehalose levels within the forager class were only detected with the GC-MS and not the HPLC method. Lastly, using the GC-MS method in the follow up study we found that trehalozin and sorbose causes a significant increase and decrease of trehalose levels respectively, in forager honey bees, independent of the glucose and fructose levels, ten minutes after injection. Taken together, these methods will provide useful tools for future studies exploring the many different physiological functional roles that trehalose can play in maintaining insect energetic homeostasis., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Hematocrit-or the percent volume of red blood cells in whole blood-is thought to fluctuate adaptively in response to changing oxygen demands that occur during different life activities and in different environments. Because red blood cells are made from materials that can be limiting, however, it is thought that hematocrit may also reflect general body condition and access to resources. We tested the effect of hydration state, resource restriction (i.e., time available to forage), and activity (i.e., different cage sizes) on hematocrit in captive red crossbills (Loxia curvirostra). We found no evidence that a mild dehydration protocol impacts hematocrit and only weak support that mild food restriction impacts hematocrit. Food restriction did, however, reduce fat deposits and fat loss was more significant in birds that were also sampled for hematocrit. Furthermore, food-restricted birds housed in flight aviaries recovered hematocrit but not fat stores following repeated blood sampling, whereas birds housed in small cages lost additional hematocrit but mitigated fat loss following successive bleeds. Together these results suggest that different flight demands may determine response to blood loss during food restriction, potentially revealing a trade-off between fat storage and red blood cell development. Our results also demonstrate the need for scientists to carefully record hematocrit data and the time course across which multiple tubes of blood are collected to avoid confounding real patterns with variation generated by sampling protocol., (© 2020 Wiley Periodicals LLC.)

Malnutrition suppresses reproductive functions in mammals, which is considered to be mostly due to the inhibition of pulsatile gonadotropin-releasing hormone (GnRH)/gonadotropin secretion. Accumulating evidence suggests that kisspeptin neurons in the arcuate nucleus (ARC) play a critical role in the regulation of pulsatile GnRH/gonadotropin release. The present study aimed to examine if the hypothalamic dynorphin A (Dyn) neurons mediate the suppression of GnRH/luteinizing hormone (LH) pulses during malnutrition. Ovariectomized rats treated with a negative feedback level of estradiol-17β-treated (OVX+E2) were administered with intravenous (iv) or fourth cerebroventricle (4V) 2-deoxy-D-glucose (2DG), an inhibitor of glucose utilization, to serve as a malnutrition model. Central administration of a Dyn receptor antagonist blocked the iv- or 4V-2DG-induced suppression of LH pulses in OVX+E2 rats. The 4V 2DG administration significantly increased the number of Pdyn (Dyn gene)-positive cells co-expressing fos in the paraventricular nucleus (PVN), but not in the ARC and supraoptic nucleus (SON), and the iv 2DG treatment significantly increased the number of fos and Pdyn-co-expressing cells in the PVN and SON, but decreased it in the ARC. The E2 treatment significantly increased Pdyn expression in the PVN, but not in the ARC and SON. Double in situ hybridization for Kiss1 (kisspeptin gene) and Oprk1 (Dyn receptor gene) revealed that around 60% of ARC Kiss1-expressing cells co-expressed Oprk1. These results suggest that the PVN Dyn neurons, at least in part, mediate LH pulse suppression induced by the hindbrain or peripheral glucoprivation, and Dyn neurons may directly suppress the ARC kisspeptin neurons in female rats., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The aim of the research was to evaluate the dynamic changes of early posthatch starvation on residual yolk absorption, synthesis of macronutrients (protein, lipid, and glycogen), and organ development in broiler chicks. A total of 720 1-day-old chicks (Lingnan Yellow) were randomly assigned to 3 treatments: group A (nonfasted), group B (fasting for 24 h after placement), and group C (fasting for 48 h after placement). The trial lasted for 168 h, and water was provided ad libitum all the time. Sampling was performed at 0, 24, 48, 72, 120, and 168 h. Nonfasting (group A) promoted (P < 0.05) the absorption of amino acids, fatty acids, mineral elements, protein, and maternal antibody in the residual yolk of broiler chicks. The concentration of insulin-like growth factor 1 in plasma and the liver was higher (P < 0.05) in group A. Nonfasting enhanced (P < 0.05) the synthesis of protein and glycogen in the breast muscle and liver; the relative weights of the liver, pancreas, and spleen; and body weight, but retarded (P < 0.05) the synthesis of triglyceride in the liver. The results indicated that nonfasting (group A) after placement promoted the absorption of residual yolk and synthesis of protein and glycogen in the breast muscle and liver, whereas early feed deprivation promoted the synthesis of lipid in the liver. Thereby, nonfasting after placement promoted organ development and body growth of broiler chicks., (Copyright © 2020. Published by Elsevier Inc.)

Starvation caused by adverse feeding stresses or food shortages has been reported to result in sleep loss in animals. However, how the starvation signal interacts with the central nervous system is still unknown. Here, the adipokinetic hormone (AKH)-Fork head Box-O (FOXO) pathway is shown to respond to energy change and adjust the sleep of Drosophila through remodeling of the s-LNv (small ventral lateral neurons) dorsal projections. Our results show that starvation prevents flies from going to sleep after the first light-dark transition. The LNvs are required for starvation-induced sleep loss through extension of the pigment dispersing factor (PDF)-containing s-LNv dorsal projections. Further studies reveal that loss of AKH or AKHR (akh receptor) function blocks starvation-induced extension of s-LNv dorsal projections and rescues sleep suppression during food deprivation. FOXO, which has been reported to regulate synapse plasticity of neurons, acts as starvation response factor downstream of AKH, and down regulation of FOXO level considerably alleviates the influence of starvation on s-LNv dorsal projections and sleep. Taking together, our results outline the transduction pathways between starvation signal and sleep, and reveal a novel functional site for sleep regulation., Competing Interests: The authors have declared that no competing interests exist.

Sleep is essential but incompatible with other behaviors, and thus sleep drive competes with other motivations. We previously showed Drosophila males balance sleep and courtship via octopaminergic neurons that act upstream of courtship-regulating P1 neurons (Machado et al., 2017). Here, we show nutrition modulates the sleep-courtship balance and identify sleep-regulatory neurons downstream of P1 neurons. Yeast-deprived males exhibited attenuated female-induced nighttime sleep loss yet normal daytime courtship, which suggests male flies consider nutritional status in deciding whether the potential benefit of pursuing female partners outweighs the cost of losing sleep. Trans-synaptic tracing and calcium imaging identified dopaminergic neurons projecting to the protocerebral bridge (DA-PB) as postsynaptic partners of P1 neurons. Activation of DA-PB neurons led to reduced sleep in normally fed but not yeast-deprived males. Additional PB-projecting neurons regulated male sleep, suggesting several groups of PB-projecting neurons act downstream of P1 neurons to mediate nutritional modulation of the sleep-courtship balance., Competing Interests: JD, VB, YZ, DM, KK No competing interests declared, (© 2020, Duhart et al.)

Nrf2 is an important transcription factor involved in the antioxidant response and is widely expressed in animal tissues. The function of Nrf2 is regulated by its negative regulator Keap1 by inducing its cytoplasmic degradation. Recent studies have suggested that Nrf2 is also regulated post-transcriptionally via miRNAs. However, to date, how miRNAs regulate Nrf2 in fish skeletal muscles is unknown. In this study, the full-length cDNAs with 2398 bp of the Nrf2 was firstly cloned by SMART RACE amplification tools from Chinese perch. The Nrf2 gene structure and its 3'-UTR region for possible miRNA binding sites, as well as its spatial expression profile were assayed. Then, we employed TargetScan Fish tool MiRNAnome to predict putative sites for five miRNAs including miR-181a-5p, MiR-194a, MiR-216a, miR-459-5p, and miR-724. Using qRT-PCR assay, we found that Nrf2 mRNA levels have negative correlation with all five miRNAs expression in muscle of nutritionally deprived fish, and that ectopic expression of miR-181a-5p alone reduces Nrf2 mRNA levels. Luciferase reporter assay in a heterologous cell system revealed that each of the five miRNAs reduced Nrf2 expression, suggesting a direct regulatory mechanism. Moreover, the miR-181a-5p suppression using specific antagomir led to a significant increase in Nrf2 expression in vivo. At the same time, the expression levels of the antioxidant enzymes CAT, ZnSOD, GPx, GSTA, and GSTA genes increased significantly after injecting miR-181a-5p antagomir. Taken together, these findings provide evidence that miRNAs are involved in the Nrf2 signaling networks in regulation of oxidative stress in fish, at least in Chinese perch muscle.