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Overweight and obesity are associated with severe metabolic disorders and an increased risk of cardiovascular diseases. It is a known fact that physical activity has a positive effect on metabolic parameters, and also reduces the risk of diseases such as diabetes. Some products can enhance the rate of lipolysis and help in improving fat loss. One of these are selective androgen receptor modulators (SARMs) which act as anabolic agents and are also believed to aid in fatburning. In this study, we investigated whether 30 days of ostarine administration could potentially improve metabolic parameters using the rat model of obesity combined with exercise. We assessed the levels of biochemical and hormonal parameters in serum samples as well as insulin sensitivity indices of tissues. There were significant changes in the metabolic parameters with exercise. However, we did not find any additive effects of ostarine and exercise on most of the parameters tested. Similar results were obtained from the analysis of gene expression and the concentration of leptin and adiponectin. Our results indicated that ostarine had a lowering effect on cholesterol concentration in the serum (P<0.05). Moreover, when combining ostarine and exercise, additive changes were only observed in the levels of total and HDL cholesterol. No significant change was observed in the metabolic parameters of obese rats with the use of ostarine at the dose of 0.4 mg/kg body weight. Since ostarine is known to enhance performance, further research on its effects is needed. [ABSTRACT FROM AUTHOR]

Hepcidin is a primary regulator of iron metabolism in the human body. By promoting ferroportin degradation, hepcidin reduces intestinal iron absorption and its release from intracellular stores. In the course of pregnancy, gradually declining hepcidin concentrations encourage placental iron transfer, thereby providing the appropriate amount of iron for fetal development. Hence, we aimed to investigate changes in maternal and cord blood hepcidin and iron metabolism parameters in normal-weight (n=17) and obese (n=17) gestating women, as well as gravid women with a history of hypothyroidism following the restoration of euthyroidism (n=17). All blood samples were taken on the day of delivery, and ELISA kits were used for measurements. A significant increase in maternal hepcidin concentration was observed in obese pregnant women, compared to normal-weight controls (29.53±4.20 ng/mL vs. 25.69±5.70 ng/mL; P<0.05). However, only a slight, insignificant tendency for lower hepcidin was noted in the hypothyroid group, compared to the healthy controls (23.10±6.00 ng/mL vs. 25.69±5.70 ng/mL; P=NS). Moreover, decreased maternal free triiodothyronine, triiodothyronine, free thyroxine, and ferritin levels were revealed in the hypothyroid group, compared to the normalweight individuals (P<0.05). Furthermore, positive correlations between maternal hepcidin and the majority of maternal thyroid hormones were found, with a most potent relation to FT3 (r=0.40; P<0.01). Interestingly, no alterations of thyroid hormones and iron metabolism parameters were noticed in cord blood in any of the subgroups. In summary, prepregnancy obesity is associated with elevated maternal hepcidin, albeit no signs of lowered cord blood iron status were shown. Medical history of hypothyroidism following the restoration of euthyroidism does not substantially influence maternal nor cord blood hepcidin concentration, as well as fetal iron homeostasis, even though free thyroid hormone levels correlate with maternal hepcidin. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Kisspeptin (KP) is a major regulator of reproductive functions. It has also been shown to be involved in the metabolic changes associated with obesity. According to the well-established concept of prenatal programming, environmental factors can influence physiological and behavioral systems at the early stages of development. Thus, we hypothesized that in pregnant women, obesity can be associated with alterations in the levels of KP. We also assumed that the observed changes in obese mothers' blood (MB) would be reflected in the umbilical cord blood (CB). MATERIALS AND METHODS: We collected MB and CB from obese and nonobese women and analyzed the differences in metabolic and hormonal profiles, including KP concentration, using commercially available assays. RESULTS: We found that the level of KP was increased in the MB and CB of obese patients compared to nonobese subjects (p<0.05). A strong correlation was observed between the concentration of KP in MB and CB (r=0.8343; p<0.01). Moreover, we detected that the differences in the adipokine profile observed in the MB were not reflected in CB. CONCLUSIONS: Our results indicate that blood KP concentration can serve as a valuable marker in pregnant women. However, further studies are needed to understand the alterations of this peptide in obese pregnant woman and their potential effects on offspring. [ABSTRACT FROM AUTHOR]

1. The aim of the present study was to investigate the effect of partial (50%) or total replacement of soybean oil (SO) by black soldier fly larvae (BSFL) fat on the growth performance, coefficients of apparent nutrient digestibility, selected internal organ weights and length, pancreatic enzyme activity and gastrointestinal tract (GIT) microecology modulation, as well as microbiota activity, physiological and immunological responses in young turkey poults. 2. A total of 216, seven day old female turkeys (B.U.T 6) were randomly distributed to three dietary treatments using six replicate pens per group with 12 birds per pen. The following design of the trial was applied: SO 100% soybean oil; BSFL50 a 50/50 combination of SO and BSFL fat; or 100% BSFL fat (total replacement of SO). 3. The use of BSFL fat did not affect the growth performance, nutrient digestibility, GIT morphology, or quality of the breast and thigh muscles. However, reduced trypsin activity was noticed in the BSFL100 group, but this had no effect on digestibility. Total replacement of SO reduced proliferation of potentially pathogenic bacteria, i.e., Enterobacteriaceae spp., as well as decreasing levels of IL-6, while partial substitution lowered the TNF-α concentration. 4. The replacement of commonly used SO by BSFL fat can be successfully applied in young turkey poult nutrition. BSFL fat may be considered an antimicrobial agent and support immune responses. [ABSTRACT FROM AUTHOR]

The objective of this research was to determine the optimal level of an encapsulated butyric acid (ButiPEARL) based on the performance of male Cobb broilers reared to 42 d of age and to investigate its effects on intestinal morphology. Experiment 1 (EXP 1) consisted of 4 treatments with 12 replicate pens that contained 45 broilers, and Experiment 2 (EXP 2) consisted of 6 treatments with 8 replicate pens that contained 50 broilers. Birds were weighed by pen on d 0, 21, 35, and 42. In EXP 1, the treatments were as follows: 1) control (C); 2) C + 100 g Buti- PEARL/ton; 3) C + 200 g ButiPEARL/ton; and 4) C + 300 g ButiPEARL/ton. In EXP 2, the treatments were identical to EXP 1, with 2 additional treatments: 5) C + 400 g ButiPEARL/ton and 6) C + 500 g Buti- PEARL/ton. In EXP 1, two 42-d-old broilers per pen were randomly selected for duodenal and jejunal tissue collection. Only the samples from the broilers fed the C or 300 g ButiPEARL treatments were analyzed for histology in EXP 1. For EXP 2, on d 21 and 35, two broilers per pen were randomly selected for duodenal, jejunal, and ileal tissue collection. For EXP 1 and 2, BW gain increased linearly with increasing butyric acid levels (P < 0.027 and P < 0.001, respectively). For EXP 1 and 2, feed conversion linearly improved with increasing butyric acid from 0 to 42 d (P < 0.001 and P < 0.001, respectively). In EXP 1, there were no differences in any intestinal morphology at 42 d between broilers fed the C or 300 g ButiPEARL treatments. In EXP 2, there were no differences in villus height at 21 or 35 d of age with any level of butyric acid. Based on the results of this research related to BW gain and feed conversion, the recommended optimum dosage level for ButiPEARL in broilers reared to 42 d of age is up to 500 g/ton. [ABSTRACT FROM AUTHOR]

Osteoporosis in menopausal women requires alternatives to current medications, considering their adverse effects. In this context, probiotics and isoflavone products are promising dietary interventions. The objective of our study was to examine the impacts of Lactobacillus acidophilus and its combination with daidzein and tempeh on calcium status, calcium transporters, and bone metabolism biomarkers in a post-menopausal osteoporotic rat model. A total of 48 female Wistar rats were exposed to a two-stage experiment involving calcium deficit induction and subsequent dietary interventions across six groups. Calcium levels, the gene expression of TRPV5 and TRPV6 calcium transporters, bone histopathology, serum bone metabolism markers, and blood biochemistry were evaluated. The results revealed that, while decreasing serum calcium levels, the groups that received the probiotic L. acidophilus and isoflavone combination exhibited increased bone metabolism biomarkers and decreased calcium transporter expressions, akin to the effects of bisphosphonate. Additionally, significant improvements in bone histopathology were observed in these groups. However, the group receiving probiotic L. acidophilus alone did not exhibit significant changes in bone resorption biomarkers, calcium transporter expression, or various blood parameters. Meanwhile, the combination of probiotic L. acidophilus with tempeh positively influenced hematological parameters and reduced cholesterol and triglyceride levels, but it led to elevated blood glucose levels. Correlation analyses highlighted associations between serum calcium levels, calcium transporter expression, and bone metabolism biomarkers. In conclusion, our findings suggest that the daily consumption of probiotic L. acidophilus in combination with isoflavone products may improve bone health in ovariectomized rats, warranting further research to elucidate potential interactions with other nutrients.

The aim of this study is to determine the influence of the mitochondrial open-reading-frame of the twelve S rRNA-c (MOTS-c) peptide on pancreatic cell physiology. Moreover, in this study, we examined the changes in MOTS-c secretion and expression under different conditions. Our experiments were conducted using laboratory cell line cultures, specifically the INS-1E and αTC-1 cell lines, which represent β and α pancreatic cells, respectively. As the pancreas is an endocrine organ, we also tested its hormone regulation capabilities. Furthermore, we assessed the secretion of MOTS-c after incubating the cells with glucose and free fatty acids. Additionally, we examined key cell culture parameters such as cell viability, proliferation, and apoptosis. The results obtained from this study show that MOTS-c has a significant impact on the physiology of pancreatic cells. Specifically, it lowers insulin secretion and expression in INS-1E cells and enhances glucagon secretion and expression in αTC-1 cells. Furthermore, MOTS-c affects cell viability and apoptosis. Interestingly, insulin and glucagon affect the MOTS-c secretion as well as glucose and free fatty acids. These experiments clearly show that MOTS-c is an important regulator of pancreatic metabolism, and there are numerous properties of MOTS-c yet to be discovered., (© 2024. The Author(s).)

Ostarine is the most popular compound in the selective androgen receptor modulator group (SARMs). Ostarine is used as a physical performance-enhancing agent. The abuse of this agent in higher doses may lead to severe side effects. Here, we evaluate the effects of ostarine on the heart. We utilized a cardiomyocyte H9C2 cell line, isolated primary female and male cardiac fibroblast cells, as well as hearts obtained from rats. Ostarine increased the accumulation of two fibrosis protein markers, αSMA and fibronectin (p < 00.1) in male, but not in female fibroblast cells. Ostarine increased the expression of the cardiomyopathy marker βMhc in the H9C2 cell line (p < 0.05) and in the heart in rats (p < 0.01). The unfavorable changes were observed at high ostarine doses. Moreover, a decrease in viability and an increase in cytotoxicity marker LDH were observed already at lowest dose (1 nmoL/l). Taken together, our results suggest that ostarine is cardiotoxic which may be more relevant in males than in females., 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 Authors. Published by Elsevier B.V. All rights reserved.)

GIP&#95;HUMAN [22-51] is a recently discovered peptide that shares the same precursor molecule with glucose-dependent insulinotropic polypeptide (GIP). In vivo, chronic infusion of GIP&#95;HUMAN [22-51] in ApoE-/- mice enhanced the development of aortic atherosclerotic lesions and upregulated inflammatory and proatherogenic proteins. In the present study, we evaluate the effects of GIP&#95;HUMAN [22-51] on insulin mRNA expression and secretion in insulin-producing INS-1E cells and isolated rat pancreatic islets. Furthermore, we characterize the influence of GIP&#95;HUMAN [22-51] on cell proliferation and death and on Nf-kB nuclear translocation. Rat insulin-producing INS-1E cells and pancreatic islets, isolated from male Wistar rats, were used in this study. Gene expression was evaluated using real-time PCR. Cell proliferation was studied using a BrdU incorporation assay. Cell death was quantified by evaluating histone-complexed DNA fragments. Insulin secretion was determined using an ELISA test. Nf-kB nuclear translocation was detected using immunofluorescence. GIP&#95;HUMAN [22-51] suppressed insulin ( Ins1 and Ins2 ) in INS-1E cells and pancreatic islets. Moreover, GIP&#95;HUMAN [22-51] promoted the translocation of NF-κB from cytoplasm to the nucleus. In the presence of a pharmacological inhibitor of NF-κB, GIP&#95;HUMAN [22-51] was unable to suppress Ins2 mRNA expression. Moreover, GIP&#95;HUMAN [22-51] downregulated insulin secretion at low (2.8 mmol/L) but not high (16.7 mmol/L) glucose concentration. By contrast, GIP&#95;HUMAN [22-51] failed to affect cell proliferation and apoptosis. We conclude that GIP&#95;HUMAN [22-51] suppresses insulin expression and secretion in pancreatic β cells without affecting β cell proliferation or apoptosis. Notably, the effects of GIP&#95;HUMAN [22-51] on insulin secretion are glucose-dependent.

Spexin (SPX) is a peptide that plays an important role in the regulation of food intake and body weight (BW) by the effect on carbohydrate-lipid metabolism. However, the role of SPX in fetal life, in children, and in adolescent metabolism is limited. Therefore, we decided to check whether obesity affects the concentration of SPX in the mother's peripheral blood (MB) and umbilical cord blood (UCB). Using MB and UCB sera on the day of delivery obtained from 48 women (24 non-obese and 24 obese) and commercially available Elisa kits and colorimetric assays, we determined changes in SPX and the relationship between SPX concentration and other metabolic and anthropometric markers (body weight and BMI) on the day of delivery and in children at the age of 36 months. We found lower concentrations of SPX in MB ( p < 0.05) and UCB ( p < 0.01) derived from obese women (BMI > 30) and a moderate linear correlation (r = 0.4429; p < 0.01) between SPX concentrations in MB and UCB. We also noted that the concentration of SPX is not correlated with the child's body weight on the day of birth (r = -0.0128). However, there is a relationship between SPX at birth and body weight at 3 years of age (r = -0.3219; p < 0.05). Based on the obtained results, it can be assumed that spexin is one of the factors modulating the child's metabolism already in the fetal period and can be considered a potential marker of future predisposition to obesity. However, confirmation of this thesis requires additional research.

Isoflavones and probiotics have shown the therapeutic potential to alter calcium absorption and bone cell metabolism. This study sought to ascertain the effect of isoflavones and probiotics on calcium status and bone health in healthy female rats. Forty-eight adult female Wistar rats were grouped and fed: a standard diet (control); and standard diets with tempeh; soy; daidzein and genistein; Lactobacillus acidophilus ; and a combination of daidzein, genistein, and L. acidophilus . The biochemical serum parameters, such as alanine transaminase, aspartate transaminase, glucose, and triacylglycerol concentrations, were measured, and calcium contents in tissues were determined. After staining the bone with hematoxylin and eosin, the number of osteoblasts, osteocytes, and the percentage of bone marrow adipocytes were counted. Compared with the control group, the soy group showed a significantly lower triacylglycerol concentration. The L. acidophilus group considerably increased the calcium content in the femoral bone. The daidzein and genistein, L. acidophilus , and a combination of daidzein, genistein, and L. acidophilus groups showed significantly lower calcium contents in the heart and kidneys. The daidzein and genistein group significantly enhanced the number of osteoblasts and osteocytes. A substantial inverse correlation was observed between calcium contents in kidneys and osteoblasts. In conclusion, the combination of daidzein, genistein, and L. acidophilus may improve bone calcium concentrations and bone cells. However, no synergistic effect between isoflavones and probiotics was detected in this study., Competing Interests: 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., (© 2023 The Authors.)

Kisspeptin, produced from the brain and peripheral tissues, may constitute an important link in metabolic regulation in response to external cues, such as diet. The kisspeptin system is well described in the brain. However, its function and regulation in the peripheral tissues, especially in relation to metabolic disease and sex differences, remain to be elucidated. As Kiss1 and Kiss1r , encoding for kisspeptin and kisspeptin receptors, respectively, are altered by overnutrition/fasting and regulated by DNA methylation during puberty and cancer, epigenetic mechanisms in metabolic disorders are highly probable. In the present study, we experimentally induced type 2 diabetes mellitus (DM2) in female Wistar rats using high-fat diet/streptozocin. We analysed expression and DNA methylation of Kiss1 and Kiss1r in the peripheral tissues, using quantitative-reverse-transcription PCR (qRT-PCR) and pyrosequencing. We discovered differential expression of Kiss1 and Kiss1r in peripheral organs in DM2 females, as compared with healthy controls, and the profile differed from patterns reported earlier in males. DM2 in females was linked to the increased Kiss1 mRNA in the liver and increased Kiss1r mRNA in the liver and adipose tissue. However, Kiss1r promoter was hypermethylated in the liver, suggesting gene silencing. Indeed, the increase in DNA methylation of Kiss1r promoter was accompanied by a reduction in Kiss1r protein, implying epigenetic or translational gene repression. Our results deliver novel evidence for tissue-specific differences in Kiss1 and Kiss1r expression in peripheral organs in DM2 females and suggest DNA methylation as a player in regulation of the hepatic kisspeptin system in DM2.

This study aimed to evaluate the effects of enriched pumpkin on calcium status in ovariectomized rats. The study was conducted in sixty female Wistar rats, which were divided into six groups: a group fed a standard diet (C) and five ovariectomized groups fed a standard diet (OVX&#95;C) or a diet with calcium lactate (CaL), with calcium lactate-enriched pumpkin (P&#95;CaL), with calcium lactate and alendronate (CaL&#95;B), or with calcium lactate-enriched pumpkin with alendronate (P&#95;CaL&#95;B). After 12 weeks of the intervention, the rats were sacrificed, and their blood and tissues were collected. The calcium concentrations in serum and in tissues were measured using flame atomic absorption spectrometry (AAS). Serum concentrations of procollagen type-1 amino-terminal propeptide (PINP), parathyroid hormone PTH, estrogen (ES), and osteocalcin (OC) were determined with enzyme-linked immunosorbent assay (ELISA). It was found that enriched pumpkin increased the calcium level in the kidneys (194.13 ± 41.01 mg) compared to the C (87.88 ± 12.42 mg) and OVX&#95;C (79.29 ± 7.66 mg) groups. The addition of alendronate increased the calcium level in the femurs (267.63 ± 23.63 mg) and more than six times in the kidneys (541.33 ± 62.91 mg) compared to the OVX&#95;C group (234.53 ± 21.67 mg and 87.88 ± 12.42 mg, respectively). We found that the CaL, P&#95;CaL, and CaL&#95;B groups had significantly lower PINP serum concentrations (4.45 ± 0.82 ng/mL, 4.14 ± 0.69 ng/mL, and 3.77 ± 0.33 ng/mL) and higher PTH serum levels (3.39 ± 0.54 ng/dL, 3.38 ± 0.57 ng/dL, and 3.47 ± 0.28 ng/dL) than the OVX&#95;C group (4.69 ± 0.82 ng/mL and 2.59 ± 0.45 ng/dL, respectively). In conclusion, pumpkin enriched with calcium lactate affects calcium status and normalizes PINP and PTH serum levels in ovariectomized rats. Diet with enriched pumpkin and alendronate increase calcium concentration in the femur. Enriched pumpkin causes calcium to accumulate in the kidneys of ovariectomized rats; alendronate significantly exacerbates this effect.

Ostarine (also known as enobosarm or Gtx-024) belongs to the selective androgen receptor modulators (SARMs). It is a substance with an aryl-propionamide structure, classified as a non-steroidal compound that is not subjected to the typical steroid transformations of aromatization and reduction by α5 reductase. Despite ongoing research on ostarine, knowledge about it is still limited. Earlier studies indicated that ostarine may affect the metabolism of muscle tissue, but this mechanism has not been yet described. We aimed to investigate the effect of ostarine on the differentiation and metabolism of muscle. Using C2C12 and L6 cells, as well as muscles obtained from rats administered ostarine, we showed that ostarine stimulates C2C12 and L6 proliferation and cell viability and that this effect is mediated by androgen receptor (AR) and ERK1/2 kinase activation (p < 0.01). We also found that ostarine stimulates muscle cell differentiation by increasing myogenin, MyoD, and MyH expression in both types of cells (p < 0.01). Moreover, pharmacological blocking of AR inhibits the stimulatory effect of ostarine. We further demonstrated that 30 days of ostarine administration increases myogenin, MyoD, and MyH expression, as well as muscle mass, in rats (p < 0.01). Based on our research, we conclude that ostarine stimulates muscle tissue proliferation and differentiation via the androgen receptor.

SPX (spexin) and its receptors GalR2 and GalR3 (galanin receptor subtype 2 and galanin receptor subtype 3) play an important role in the regulation of lipid and carbohydrate metabolism in human and animal fat tissue. However, little is still known about the role of this peptide in the metabolism of muscle. The aim of this study was to determine the impact of SPX on the metabolism, proliferation and differentiation of the skeletal muscle cell line C2C12. Moreover, we determined the effect of exercise on the SPX transduction pathway in mice skeletal muscle. We found that increased SPX, acting via GalR2 and GalR3 receptors, and ERK1/2 phosphorylation stimulated the proliferation of C2C12 cells ( p < 0.01). We also noted that SPX stimulated the differentiation of C2C12 by increasing mRNA and protein levels of differentiation markers Myh, myogenin and MyoD ( p < 0.01). SPX consequently promoted myoblast fusion into the myotubule ( p < 0.01). Moreover, we found that, in the first stage (after 2 days) of myocyte differentiation, GalR2 and GalR3 were involved, whereas in the last stage (day six), the effect of SPX was mediated by the GalR3 isoform. We also noted that exercise stimulated SPX and GalR2 expression in mice skeletal muscle as well as an increase in SPX concentration in blood serum. These new insights may contribute to a better understanding of the role of SPX in the metabolism of skeletal muscle.

Background: This study aimed to evaluate spexin as a novel blood marker and to describe the relationship of this peptide with selected biochemical metabolites measured during the transition period in dairy cows. Additionally, mRNA expression of the spexin gene as well as spexin receptors - galanin receptor type 2 and galanin receptor type 3, was investigated in several bovine tissues. Blood samples were collected at weekly intervals starting at 21 days before the estimated parturition day until 21 days in milk to determine concentrations of spexin, nonesterified fatty acids, β-hydroxybutyrate acid, total and active ghrelin, progesterone, glucose, insulin, IGF-I, triglycerides, cholesterol, leptin, corticosterone and 17-β-estradiol as well as the activity of aspartate transaminase, alkaline phosphatase and gamma-glutamyl transferase., Results: Spexin concentration decreased from 21 d before parturition to calving day and next it rose during the first 14 d of lactation. The lowest concentration of spexin was recorded on the calving day and it differed from the mean level of this peptide before parturition as well as postpartum. Moreover, differences were observed between mean spexin concentrations before and after calving. Spexin levels were moderately negatively correlated with NEFA (r = - 0.39) and total ghrelin contents (r = - 0.41), weakly correlated with BHBA (r = - 0.35) while they showed a moderate positive relationship with progesterone concentrations (r = 0.42). Moreover, we detected that mRNA expression of GALR2, GALR3 and SPX is present in various bovine tissues (kidney, bowel, rumen, spinal cord, lung, skeletal muscle, liver, heart, fat and spleen)., Conclusion: A negative correlation between spexin concentration and NEFA, BHBA and total ghrelin contents as well as a positive relationship with levels of progesterone, metabolites and hormones, which are key players in the dairy cow transition period, may confirm an important function of this peptide in metabolism regulation. Thus measurement of spexin concentration could provide useful supplementary information for dairy cow herd health monitoring., (© 2021. The Author(s).)

MOTS-c peptide is a member of the group of mitochondria-derived peptides (MDP). It is a product of the open reading frame in the 12S RNA gene. Due to its features and functions in the body, this peptide is classified as a hormone. The first publications indicated that this hormone improves insulin sensitivity and lowers body weight in obese animals. This suggests that it may be an important peptide in maintaining the body's energy homeostasis. The aim of our work was to investigate the potential role of MOTS-c peptide during pregnancy, which is a condition prone to metabolic disorders. The research covered healthy, obese women and women with thyroid disorders. The obtained results indicated an increase in the concentration of MOTS-c in the blood of mothers and newborns in the obese group as compared to the healthy control group and a corresponding decrease in the concentration of this peptide in mothers and newborns in the group with hypothyroidism compared to the obese group. Moreover, we also observed a strong positive correlation between the concentration of MOTS-c in maternal blood and in umbilical cord blood. In summary, the MOTS-c peptide shows changes in blood concentration in various physiological states and may, in the future, become an important tool in the fight against metabolic diseases such as obesity or type 2 diabetes.

Spexin (SPX) is a 14 aa peptide discovered in 2007 using bioinformatics methods. SPX inhibits food intake and regulates lipid, and carbohydrate metabolism. Here, we evaluate the ability of SPX at improving metabolic control and liver function in obese and type 2 diabetic animals. The effects of 30 days SPX treatment of mice with experimentally induced obesity (DIO) or type 2 diabetes (T2DM) on serum glucose and lipid levels, insulin sensitivity and hormonal profile (insulin, glucagon, adiponectin, leptin, TNF alpha, IL-6 and IL-1β) are characterized. In addition, alterations of hepatic lipid and glycogen contents are evaluated. We report that SPX decreases body weight in healthy and DIO mice, and reduces lipid content in all three animal groups. SPX improves insulin sensitivity in DIO and T2DM animals. In addition, SPX modulates hormonal and metabolic profile by regulating the concentration of adiponectin (concentration increase) and leptin (concentration decrease) in the serum blood of DIO and T2DM mice. Lastly, SPX decreases lipid content as well as IL-6 and TNF-α protein levels in liver of DIO and T2DM mice, and reduces IL-6 and TNF-alpha concentrations in the serum derived from T2DM mice. Based on our results, we conclude that SPX could be involved in the development of obesity and type 2 diabetes mellitus and it can be further evaluated as a potential target for therapy of DIO and T2DM., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Peptide hormones play a prominent role in controlling energy homeostasis and metabolism. They have been implicated in controlling appetite, the function of the gastrointestinal and cardiovascular systems, energy expenditure, and reproduction. Furthermore, there is growing evidence indicating that peptide hormones and their receptors contribute to energy homeostasis regulation by interacting with white and brown adipose tissue. In this article, we review and discuss the literature addressing the role of selected peptide hormones discovered in the 21st century (adropin, apelin, elabela, irisin, kisspeptin, MOTS-c, phoenixin, spexin, and neuropeptides B and W) in controlling white and brown adipogenesis. Furthermore, we elaborate how these hormones control adipose tissue functions in vitro and in vivo.

The increasing prevalence of overweight and obesity and the rising awareness of their negative consequences are forcing researchers to take a new view of nutrition and its consequences for the metabolism of whole organisms as well as the metabolism of their individual systems and cells. Despite studies on nutrition having been carried out for a few decades, not many of them have focused on the impacts of these diets on changes in the metabolism and endocrine functions of isolated adipocytes. Therefore, we decided to investigate the effects of the long-term use (60 and 120 days) of a high-fat diet (HFD) and of a high-protein diet (HPD) on basic metabolic processes in fat cells-lipogenesis, lipolysis, and glucose uptake-and endocrine function, which was determined according to the secretion of adipokines into the incubation medium. Our results proved that the HPD diet improved insulin sensitivity, increased the intracellular uptake of glucose ( p < 0.01) and its incorporation into lipids ( p < 0.01) and modulated the endocrine function of these cells (decreasing leptin secretion; p < 0.01). The levels of biochemical parameters in the serum blood also changed in the HPD-fed rats. The effects of the HFD were inverse, as expected. We observed a decrease in adiponectin secretion and a diminished rate of lipogenesis ( p < 0.01). Simultaneously, the secretion of leptin and resistin ( p < 0.01) from isolated adipocytes increased. In conclusion, we noted that the long-term use of HPD and HFD diets modulates the metabolism and endocrine functions of isolated rat adipocytes. We summarize that an HFD had a negative effect on fat tissue functioning, whereas an HPD had positive results, such as increased insulin sensitivity and an improved metabolism of glucose and lipids in fat tissue. Moreover, we noticed that negative metabolic changes are reflected more rapidly in isolated cells than in the metabolism of the whole organism.

Resveratrol is a biologically active diphenolic compound exerting multiple beneficial effects in the organism, including anti-diabetic properties. This action is, however, not fully elucidated. In the present study, we examined effects of resveratrol on some parameters related to insulin signaling, and also on diabetes-associated dysregulation in Goto-Kakizaki (GK) rats with congenital type 2 diabetes. Resveratrol was given at the dose of 20 mg/kg b.w. for 10 weeks. It was shown that the expression and phosphorylation levels of insulin receptor in the skeletal muscle of GK rats were significantly decreased, compared with control animals. However, these changes were totally prevented by resveratrol. Liver expression of the insulin receptor was also reduced, but in this case, resveratrol was ineffective. Resveratrol was also demonstrated to significantly influence parameters of insulin binding (dissociation constant and binding capacity) in the skeletal muscle and liver. Moreover, it was shown that the expression levels of proteins related to intracellular glucose transport (GLUT4 and TUG) in adipose tissue of GK rats were significantly decreased. However, treatment with resveratrol completely abolished these changes. Resveratrol was found to induce normalization of TUG expression in the skeletal muscle. Blood levels of insulin and GIP were elevated, whereas proinsulin and GLP-1 diminished in GK rats. However, concentrations of these hormones were not affected by resveratrol. These results indicate that resveratrol partially ameliorates diabetes-associated dysregulation in GK rats. The most relevant finding covers the normalization of the insulin receptor expression in the skeletal muscle and also GLUT4 and TUG in adipose tissue.

Spexin (SPX) is a highly conservative peptide hormone containing 14 amino acids and was discovered in 2007 by bioinformatics methods. However, nothing is yet known about its role in the metabolism of birds, including broilers. The aim of this study was to investigate the effect of short-term fasting (2, 4, and 8 h) on the concentration of SPX in blood serum and the expression levels of the genes encoding this peptide ( SPX1 ) and its receptors, GALR2 and GALR3, in the tissues involved in carbohydrate and lipid metabolism (muscles, adipose tissue, and liver). We also analyzed the mRNA expression of these genes in various chicken tissues. Moreover, we studied the correlation between the serum level of SPX and other metabolic parameters (insulin, glucagon, glucose, triglycerides, and cholesterol). Using RT-qPCR, we found that SPX1, GALR2, and GALR3 are expressed in all investigated tissues in broiler chicken. Moreover, using a commercially available radio-immunoassay, we noted an increase of the SPX level in blood serum after 4 and 8 h of fasting compared to nonfasted animals ( p < 0.05). This increase was positively correlated with glucagon concentration (r = 0.341; p < 0.05) and negatively with glucose concentration (r = -0.484; p < 0.01). Additionally, we discovered that in the short term, food deprivation leads to the expression regulation of SPX1 , GALR2, and GLAR3 in tissues associated with metabolism of carbohydrates and lipids. The obtained results indicate that SPX is involved in the regulation of metabolism in broiler chickens.

Lithium has been the most important mood stabilizer used for the treatment of bipolar disorder and prophylaxis of manic and depressive episodes. Despite long use in clinical practice, the exact molecular mechanisms of lithium are still not well identified. Previous experimental studies produced inconsistent results due to different duration of lithium treatment and using animals without manic-like or depressive-like symptoms. Therefore, we aimed to analyze the gene expression profile in three brain regions (amygdala, frontal cortex and hippocampus) in the rat model of mania and depression during chronic lithium administration (2 and 4 weeks). Behavioral changes were verified by the forced swim test, open field test and elevated maze test. After the experiment, nucleic acid was extracted from the frontal cortex, hippocampus and amygdala. Gene expression profile was done using SurePrint G3 Rat Gene Expression whole transcriptome microarrays. Data were analyzed using Gene Spring 14.9 software. We found that chronic lithium treatment significantly influenced gene expression profile in both mania and depression models. In manic rats, chronic lithium treatment significantly influenced the expression of the genes enriched in olfactory and taste transduction pathway and long non-coding RNAs in all three brain regions. We report here for the first time that genes regulating olfactory and taste receptor pathways and long non-coding RNAs may be targeted by chronic lithium treatment in the animal model of mania.

Background: Spexin (SPX) is a peptide hormone that regulates body weight, adipose tissue metabolism, and food intake., Hypothesis: Serum SPX concentration correlates with body condition score (BCS) and markers of obesity in dogs., Animals: Fifty-seven dogs of varying body condition assessed using a 5-point BCS., Methods: Prospective, nonblinded, observational cohort study. Serum SPX concentration was measured using commercially available radioimmunoassay (RIA) in dogs with varying BCS. Spexin mRNA and protein expression were detected using real-time quantitative polymerase chain reaction and immunofluorescence staining., Results: Serum SPX concentration was lower in dogs with BCS4 (8.56 +/- 2.86) and BCS5 (6.7 +/- 2.12) compared to BCS2 (11.96 +/- 2.23) and BCS3 (10.51 +/- 2.19; BCS2 vs BCS5, P < .001 and BCS2 vs BCS4, P = .005; BCS3 vs BCS5, P = .002). Spexin mRNA was detected in adipose tissue, liver and pancreas. Spexin protein was expressed in adipose tissue and liver but not in pancreas. There were negative correlations between SPX and serum concentration of insulin (P < .05); leptin (P < .01), triglycerides (P < .01), total cholesterol (P < .01), nonesterified fatty acids (P < .01), and fructosamine (P < .01). There was a positive correlation between SPX and serum concentration of adiponectin (P < .01)., Conclusions and Clinical Importance: Spexin could be involved in pathogenesis of obesity in dogs, and might be considered as a potential marker for obesity., (© 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC. on behalf of the American College of Veterinary Internal Medicine.)

The present study aimed to characterize the role of spexin (SPX) in maintaining glucose and lipid homeostasis in vivo in rats with diet-induced obesity. The in vitro effect of spexin on metabolic and endocrine functions of adipocytes isolated from obese rats was also investigated. The in vivo experiment was conducted on rats with diet-induced obesity and administered with SPX for 7 days. Lipid and carbohydrate parameters, liver markers, and hormonal profile were measured. In in vitro studies, adipocytes isolated from obese rats were used. The effect of SPX on lipolysis, lipogenesis, and leptin secretion from fat cells was assessed. The results showed that short-term administration of SPX causes weight loss, increases insulin sensitivity, and improves the metabolic state of obese rats. The in vitro experiments showed that spexin and its receptors, namely galanin receptor 2 (GALR2) and galanin receptor 3 (GALR3), were expressed in various fat depots and in adipocytes from obese rats. We also found that the addition of spexin increased the basal and isoproterenol-stimulated lipolysis and reduced the basal and insulin-stimulated lipogenesis in adipocytes isolated from obese rats. Molecular analysis showed that SPX activated hormone-sensitive lipase (HSL) phosphorylation and upregulated perilipin and HSL mRNA expression. These results suggest that SPX regulates metabolism of obese rats by affecting lipolysis and lipogenesis in adipocytes. Moreover, the present study for the first time demonstrates that SPX modulates leptin synthesis and secretion from isolated adipocytes., (Copyright © 2020 Elsevier Inc. All rights reserved.)