Search

Background: Exposure to early life stress (ELS) and maternal consumption of a high-fat and high-sugar diet can have detrimental effects on adult emotional responses. The microbiota and gut-brain axis have been proposed as playing a mediating role in the regulation of stress and emotion. Method: Young male rats were exposed to maternal separation (MS) together with maternal and postnatal consumption of a HFS diet (45%kcal saturated fat, 17%kcal sucrose). Anxiety-like behaviour was evaluated using an elevated zero-maze, and depression-like behaviour using the forced-swim and sucrose preference tests. Microbiota composition and derived metabolites were also analysed in faecal samples using a gas chromatograph and mass spectrometry. Results: Combined exposure to MS and lifelong consumption of a HFS diet partially reversed the abnormal anxiety-like and depression-like behaviours in early adulthood caused by each adverse factor alone. Diet composition had a greater negative impact than ELS exposure on the gut microbiota, and both environmental factors interacted with microbiota composition partially counteracting their negative effects. Conclusions: The effects of exposure to early life stress and a HFS diet independently are partially reversed after the combination of both factors. These results suggest that ELS and diet interact to modulate adult stress response and gut microbiota. [ABSTRACT FROM AUTHOR]

The escalating prevalence of metabolic diseases and an aging demographic has been correlated with a concerning rise in Alzheimer's disease (AD) incidence. This study aimed to access the protective effects of curcumin, a bioactive flavonoid from turmeric, on spatial memory, metabolic functions, and the regulation of the gut microbiome in AD-induced (3xTg-AD) mice fed with either a normal chow diet (NCD) or a high-fat high-sugar diet (HFHSD). Our findings revealed an augmented susceptibility of the HFHSD-fed 3xTg-AD mice for weight gain and memory impairment, while curcumin supplementation demonstrated a protective effect against these changes. This was evidenced by significantly reduced body weight gain and improved behavioral and cognitive function in the curcumin-treated group. These improvements were substantiated by diminished fatty acid synthesis, altered cholesterol metabolism, and suppressed adipogenesis-related pathways in the liver, along with modified synaptic plasticity-related pathways in the brain. Moreover, curcumin enriched beneficial gut microbiota, including Oscillospiraceae and Rikenellaceae at the family level, and Oscillibacter, Alistipes, Pseudoflavonifractor, Duncaniella, and Flintibacter at the genus level. The observed alteration in these gut microbiota profiles suggests a potential crosswalk in the liver and brain for regulating metabolic and cognitive functions, particularly in the context of obesity-associated cognitive disfunction, notably AD. [ABSTRACT FROM AUTHOR]

Background: The consumption of high‐caloric diets strongly contributes to the development of non‐communicable diseases (NCDs), including cardiovascular disease, the leading cause of mortality worldwide. Exercise (along with diet intervention) is one of the primary non‐pharmacological approaches to promote a healthier lifestyle and counteract the rampant prevalence of NCDs. The present study evaluated the effects of exercise cessation after a short period training on the cardiac metabolic and mitochondrial function of female rats. Methods: Seven‐week‐old female Sprague–Dawley rats were fed a control or a high‐fat, high‐sugar (HFHS) diet and, after 7 weeks, the animals were kept on a sedentary lifestyle or submitted to endurance exercise for 3 weeks (6 days per week, 20–60 min/day). The cardiac samples were analysed 8 weeks after exercise cessation. Results: The consumption of the HFHS diet triggered impaired glucose tolerance, whereas the HFHS diet and physical exercise resulted in different responses in plasma adiponectin and leptin levels. Cardiac mitochondrial respiration efficiency was decreased by the HFHS diet consumption, which led to reduced ATP and increased NAD(P)H mitochondrial levels, which remained prevented by exercise 8 weeks after cessation. Exercise training‐induced cardiac adaptations in redox balance, namely increased relative expression of Nrf2 and downstream antioxidant enzymes persist after an eight‐week exercise cessation period. Conclusions: Endurance exercise modulated cardiac redox balance and mitochondrial efficiency in female rats fed a HFHS diet. These findings suggest that exercise may elicit cardiac adaptations crucial for its role as a non‐pharmacological intervention for individuals at risk of developing NCDs. [ABSTRACT FROM AUTHOR]

Obesity is a major contributor to the silent and progressive development of type 2 diabetes (T2D) whose prevention could be improved if individuals at risk were identified earlier. Our aim is to identify early phenotypes that precede T2D in diet-induced obese minipigs. We fed four groups of minipigs (n = 5–10) either normal-fat or high-fat high-sugar diet during 2, 4, or 6 months. Morphometric features were recorded, and metabolomics and clinical parameters were assessed on fasting plasma samples. Multivariate statistical analysis on 46 morphometrical and clinical parameters allowed to differentiate 4 distinct phenotypes: NFC (control group) and three others (HF2M, HF4M, HF6M) corresponding to the different stages of the obesity progression. Compared to NFC, we observed a rapid progression of body weight and fat mass (4-, 7-, and tenfold) in obese phenotypes. Insulin resistance (IR; 2.5-fold increase of HOMA-IR) and mild dyslipidemia (1.2- and twofold increase in total cholesterol and HDL) were already present in the HF2M and remained stable in HF4M and HF6M. Plasma metabolome revealed subtle changes of 23 metabolites among the obese groups, including a progressive switch in energy metabolism from amino acids to lipids, and a transient increase in de novo lipogenesis and TCA-related metabolites in HF2M. Low anti-oxidative capacities and anti-inflammatory response metabolites were found in the HF4M, and a perturbed hexose metabolism was observed in HF6M. Overall, we show that IR and progressively obese minipigs reveal phenotype-specific metabolomic signatures for which some of the identified metabolites could be considered as potential biomarkers of early progression to TD2. [ABSTRACT FROM AUTHOR]

The escalating prevalence of metabolic diseases and an aging demographic has been correlated with a concerning rise in Alzheimer’s disease (AD) incidence. This study aimed to access the protective effects of curcumin, a bioactive flavonoid from turmeric, on spatial memory, metabolic functions, and the regulation of the gut microbiome in AD-induced (3xTg-AD) mice fed with either a normal chow diet (NCD) or a high-fat high-sugar diet (HFHSD). Our findings revealed an augmented susceptibility of the HFHSD-fed 3xTg-AD mice for weight gain and memory impairment, while curcumin supplementation demonstrated a protective effect against these changes. This was evidenced by significantly reduced body weight gain and improved behavioral and cognitive function in the curcumin-treated group. These improvements were substantiated by diminished fatty acid synthesis, altered cholesterol metabolism, and suppressed adipogenesis-related pathways in the liver, along with modified synaptic plasticity-related pathways in the brain. Moreover, curcumin enriched beneficial gut microbiota, including Oscillospiraceae and Rikenellaceae at the family level, and Oscillibacter, Alistipes, Pseudoflavonifractor, Duncaniella, and Flintibacter at the genus level. The observed alteration in these gut microbiota profiles suggests a potential crosswalk in the liver and brain for regulating metabolic and cognitive functions, particularly in the context of obesity-associated cognitive disfunction, notably AD.

Background: Excess adipose tissue accumulation and obesity are characterised by chronic, low-grade, systemic inflammation. Nestfatin-1 is a neuropeptide derived from the precursor protein nucleobindin-2 (NUCB2), which was initially reported to exert anorexigenic effects. The present study aimed to investigate the effects of an obesogenic diet (OD; high-fat, high-sugar) in NUCB2 knockout (KO) mice and of nesfatin-1 treatment in LPS-stimulated 3T3-L1 preadipocytes. Methods: Subcutaneous white adipose tissue (Sc-WAT) samples from wild type (WT) and NUCB2 KO mice that were fed a normal diet (ND), or the OD for 12 weeks were used for RNA and protein extraction, as well as immunohistochemistry. 3T3-L1 cells were treated with 100 nM nesfatin-1 during differentiation and stimulated with 1 µg/mL LPS for measuring the expression and secretion of pro-inflammatory mediators by qPCR, western blotting, immunofluorescence, Bioplex, and ELISA. Results: Following the OD, the mRNA, protein and cellular expression of pro-inflammatory mediators (Tnfα, Il-6, Il-1β, Adgre1, Mcp1, TLR4, Hmbgb1 and NF-kB) significantly increased in the ScWAT of NUCB2 KO mice compared to ND controls. Adiponectin and Nrf2 expression significantly decreased in the ScWAT of OD-fed NUCB2 KO, without changes in the OD-fed WT mice. Furthermore, nesfatin-1 treatment in LPS-stimulated 3T3-L1 cells significantly reduced the expression and secretion of pro-inflammatory cytokines (Tnfα, Il-6, Il-1β, Mcp1) and hmgb1. Conclusion: An obesogenic diet can induce significant inflammation in the ScWAT of NUCB2 KO mice, involving the HMGB1, NRF2 and NF-kB pathways, while nesfatin-1 reduces the pro-inflammatory response in LPS-stimulated 3T3-L1 cells. These findings provide a novel insight into the metabolic regulation of inflammation in WAT. [ABSTRACT FROM AUTHOR]

Purpose: Maternal nutrition during early development and paternal nutrition pre-conception can programme offspring health status. Hypothalamus adipose axis is a target of developmental programming, and paternal and maternal high-fat, high-sugar diet (HFS) may be an important factor that predisposes offspring to develop obesity later in life. This study aims to investigate Wistar rats' maternal and paternal HFS differential contribution on the development, adiposity, and hypothalamic inflammation in male offspring from weaning until adulthood. Methods: Male progenitors were fed a control diet (CD) or HFS for 10 weeks before mating. After mating, dams were fed CD or HFS only during pregnancy and lactation. Forming the following male offspring groups: CD—maternal and paternal CD; MH—maternal HFS and paternal CD; PH—maternal CD and paternal HFS; PMH—maternal and paternal HFS. After weaning, male offspring were fed CD until adulthood. Results: Maternal HFS diet increased weight, visceral adiposity, and serum total cholesterol levels, and decreased hypothalamic weight in weanling male rats. In adult male offspring, maternal HFS increased weight, glucose levels, and hypothalamic NFκBp65. Paternal HFS diet lowered hypothalamic insulin receptor levels in weanling offspring and glucose and insulin levels in adult offspring. The combined effects of maternal and paternal HFS diets increased triacylglycerol, leptin levels, and hypothalamic inflammation in weanling rats, and increased visceral adiposity in adulthood. Conclusion: Male offspring intake of CD diet after weaning reversed part of the effects of parental HFS diet during the perinatal period. However, maternal and paternal HFS diet affected adiposity and hypothalamic inflammation, which remained until adulthood. [ABSTRACT FROM AUTHOR]

Compulsive forms of eating displayed by some obese individuals share similarities with compulsive drug‐taking behaviour, a hallmark feature of substance use disorder. This raises the possibility that drug addiction treatments may show utility in the treatment of compulsive overeating. N‐Acetylcysteine (NAC) is a cysteine pro‐drug which has experienced some success in clinical trials, reducing cocaine, marijuana and cigarette use, as well as compulsive behaviours such as gambling and trichotillomania. We assessed the impact of NAC on addiction‐like behaviour towards highly palatable food in a rat model of diet‐induced obesity. Adult male Sprague–Dawley rats were placed on a high‐fat high‐sugar diet for 8 weeks and then assigned to diet‐induced obesity‐prone (DIO) or diet‐induced obesity‐resistant (DR) groups based on weight gain. DIO and DR rats were subjected to an operant conditioning paradigm whereby rats could lever press for high‐fat high‐sugar food pellets. This alternated with periods of signalled reward unavailability. Before treatment DIO rats ate more in their home cage, earned more food pellets in operant sessions, and responded more during periods that signalled reward unavailability (suggestive of compulsive‐like food seeking) compared with DR rats. This persistent responding in the absence of reward displayed by DIO rats was ameliorated by daily injections of NAC (100 mg/kg, i.p.) for 14 days. By the end of the treatment period, lever‐pressing by NAC‐treated DIO rats resembled that of DR rats. These findings suggest that NAC reduces addiction‐like behaviour towards food in rats and supports the potential use of this compound in compulsive overeating. [ABSTRACT FROM AUTHOR]

Although adverse early experiences prime individuals to be at increased risk for chronic pain, little research has examined the trauma-pain relationship in early life or the underlying mechanisms that drive pathology over time. Given that early experiences can potentiate the nociceptive response, this study aimed to examine the effects of a high-fat, high-sugar (HFHS) diet and early life stress (maternal separation [MS]) on pain outcomes in male and female adolescent rats. Half of the rats also underwent a plantar-incision surgery to investigate how the pain system responded to a mildly painful stimuli in adolescence. Compared with controls, animals that were on the HFHS diet, experienced MS, or had exposure to both, exhibited increased anxiety-like behavior and altered thermal and mechanical nociception at baseline and following the surgery. Advanced magnetic resonance imaging demonstrated that the HFHS diet and MS altered the maturation of the brain, leading to changes in brain volume and diffusivity within the anterior cingulate, amygdala, corpus callosum, nucleus accumbens, and thalamus, while also modifying the integrity of the corticospinal tracts. The effects of MS and HFHS diet were often cumulative, producing exacerbated pain sensitivity and increased neurobiological change. As early experiences are modifiable, understanding their role in pain may provide targets for early intervention/prevention. [ABSTRACT FROM AUTHOR]

Background: Excess adipose tissue accumulation and obesity are characterised by chronic, low-grade, systemic inflammation. Nestfatin-1 is a neuropeptide derived from the precursor protein nucleobindin-2 (NUCB2), which was initially reported to exert anorexigenic effects. The present study aimed to investigate the effects of an obesogenic diet (OD; high-fat, high-sugar) in NUCB2 knockout (KO) mice and of nesfatin-1 treatment in LPS-stimulated 3T3-L1 preadipocytes. Methods: Subcutaneous white adipose tissue (Sc-WAT) samples from wild type (WT) and NUCB2 KO mice that were fed a normal diet (ND), or the OD for 12 weeks were used for RNA and protein extraction, as well as immunohistochemistry. 3T3-L1 cells were treated with 100 nM nesfatin-1 during differentiation and stimulated with 1 µg/mL LPS for measuring the expression and secretion of pro-inflammatory mediators by qPCR, western blotting, immunofluorescence, Bioplex, and ELISA. Results: Following the OD, the mRNA, protein and cellular expression of pro-inflammatory mediators (Tnfα, Il-6, Il-1β, Adgre1, Mcp1, TLR4, Hmbgb1 and NF-kB) significantly increased in the ScWAT of NUCB2 KO mice compared to ND controls. Adiponectin and Nrf2 expression significantly decreased in the ScWAT of OD-fed NUCB2 KO, without changes in the OD-fed WT mice. Furthermore, nesfatin-1 treatment in LPS-stimulated 3T3-L1 cells significantly reduced the expression and secretion of pro-inflammatory cytokines (Tnfα, Il-6, Il-1β, Mcp1) and hmgb1. Conclusion: An obesogenic diet can induce significant inflammation in the ScWAT of NUCB2 KO mice, involving the HMGB1, NRF2 and NF-kB pathways, while nesfatin-1 reduces the pro-inflammatory response in LPS-stimulated 3T3-L1 cells. These findings provide a novel insight into the metabolic regulation of inflammation in WAT.

Abstract In our modern society, the exposure to light at night (LAN) has increased considerably, which may impact human health negatively. Especially exposure to light at night containing short wavelength emissions (~450–500 nm) can disrupt the normal function of the biological clock, altering sleep‐wake cycles and inducing metabolic changes. Recently, we reported that light at night acutely impairs glucose tolerance in nocturnal rats. However, light at night in nocturnal rodents coincides with their activity period, in contrast to artificial light at night exposure in humans. The aim of this study was to evaluate the acute effects of blue (λ = 490 ± 20 nm) artificial light at night (bALAN) on glucose metabolism and food intake in both male and female diurnal Sudanian grass rats (Arvicanthis ansorgei) fed either regular chow or a free choice high‐fat high sucrose diet (HFHS). In both chow and HFHS fed male Arvicanthis, 1‐hour of bALAN exposure induced a higher glucose response in the oral glucose tolerance test (OGTT) accompanied by a significant decrease in plasma insulin. Furthermore, in HFHS fed animals, bALAN induced an increase in sucrose intake during the dark phase in males but not in females. Additionally, 1‐h of bALAN increased the nonfasted glucose levels together with plasma corticosterone in female grass rats. These results provide new and further evidence for the deleterious effects of exposure to short wavelength emission‐containing artificial light at night on glucose metabolism in a diurnal rodent in a sex‐dependent manner.

Obesity is recognized worldwide as a complex metabolic disorder that has reached epidemic proportions and is often associated with a high incidence of cardiovascular diseases. To study this pathology and evaluate cardiac function, several models of diet-induced obesity (DIO) have been developed. The Western diet (WD) is one of the most widely used models; however, variations in diet composition and time period of the experimental protocol make comparisons challenging. Thus, this study aimed to evaluate the effects of two different types of Western diet on cardiac remodeling in obese rats with sequential analyses during a long-term follow-up. Male Wistar rats were distributed into three groups fed with control diet (CD), Western diet fat (WDF), and Western diet sugar (WDS) for 41 weeks. The animal nutritional profile and cardiac histology were assessed at the 41st week. Cardiac structure and function were evaluated by echocardiogram at four different moments: 17, 25, 33, and 41 weeks. A noninvasive method was performed to assess systolic blood pressure at the 33rd and 41st week. The animals fed with WD (WDF and WDS) developed pronounced obesity with an average increase of 86.5% in adiposity index at the end of the experiment. WDF and WDS groups also presented hypertension. The echocardiographic data showed no structural differences among the three groups, but WDF animals presented decreased endocardial fractional shortening and ejection fraction at the 33rd and 41st week, suggesting altered systolic function. Moreover, WDF and WFS animals did not present hypertrophy and interstitial collagen accumulation in the left ventricle. In conclusion, both WD were effective in triggering severe obesity in rats; however, only the WDF induced mild cardiac dysfunction after long-term diet exposure. Further studies are needed to search for an appropriate DIO model with relevant cardiac remodeling.

Hyperlipidemia is the root cause for development of atherosclerosis, coronary heart disease, diabetes mellitus, obesity, hypertension and cerebral palsy. Cymbopogon jwarancusa is an aromatic grass (Rusha grass, khavi grass) belonging to family Poaceaea. C. jwarancusa essential oil is famous for its use in perfumery, soaps cosmetics, detergents, medicine and pharmaceuticals. The anti-pyretic, anti-fungal, antibacterial, anti-oxidant and cytotoxic activities of C. jwarancusa have been reported in literature. In the present study different doses of C. jwarancusa extract have been investigated for anti-hyperlipidemic and anti-hyperglycemic activities in high-fat high sugar diet model in rats. Hyperlipidemia and hyperglycemia were assessed by measuring body weight, serum lipid profile and fasting blood glucose levels. Administration of ethanol leaves extract of C. jwarancusa exhibited significant dose-dependent reduction in body weight, lipid parameters and blood sugar levels. Hence it may be concluded that C. jwarancusa aids in ameliorating hyperlipidemic, hyperglycemic conditions and has potential to reduce the risk of cardiovascular problems. [ABSTRACT FROM AUTHOR]

Diabetes and the related disease metabolic syndrome are epidemic in the United States, in part due to a shift in diet and decrease in physical exercise. PAS kinase is a sensory protein kinase associated with many of the phenotypes of these diseases, including hepatic triglyceride accumulation and metabolic dysregulation in male mice placed on a high-fat diet. Herein we provide the first characterization of the effects of western diet (high-fat high-sugar, HFHS) on Per-Arnt-Sim kinase mice (PASK−/−) and the first characterization of both male and female PASK−/− mice. Soleus muscle from the PASK−/− male mice displayed a 2-fold higher oxidative phosphorylation capacity than wild type (WT) on the normal chow diet. PASK−/− male mice were also resistant to hepatic triglyceride accumulation on the HFHS diet, displaying a 2.7-fold reduction in hepatic triglycerides compared to WT mice on the HFHS diet. These effects on male hepatic triglyceride were further explored through mass spectrometry-based lipidomics. The absence of PAS kinase was found to affect many of the 44 triglycerides analyzed, preventing hepatic triglyceride accumulation in response to the HFHS diet. In contrast, the female mice showed resistance to hepatic triglyceride accumulation on the HFHS diet regardless of genotype, suggesting the effects of PAS kinase may be masked.

[Display omitted] • Parental high-fat high-sugar diet can modulate offspring commensal bacteria. • Changes in gut hormones in the GBA, may be linked to hypothalamic inflammation and increased adiposity in the offspring. • Hypothalamic Leptin resistance may be involved in reduced energy expenditure and altered energy homeostasis in the adult offspring. • Parental high-fat high-sugar diet may program offspring susceptibility to metabolic diseases, later in life, even after weaning on a healthy diet. The gut-brain axis (GBA) is implicated in the development of obesity, and its role in developmental programming needs to be explored. This study uncovers the effects of a parental high-fat, high-sugar diet (HFS) on the gut (colon) and brain (hypothalamus) GBA of male Wistar rat offspring at weaning until adulthood. For ten weeks before mating, male progenitors were fed a control diet (CD) or HFS, whereas dams were fed CD or HFS during pregnancy and lactation. Male offspring aged 21-and 90-day old were assessed for: Gene expression of toll-like receptor 4 (TLR4) pathway and zonula occludens 1 (ZO1) in the colon and hypothalamus; hypothalamic gene expression of orexigenic neuropeptides and Leptin receptor; serum levels of lipopolysaccharide (LPS), glucagon like peptide 1 (GLP-1), Ghrelin and neuropeptide Y (NPY); colonic cytokine levels; Faecal Bifidobacterium spp. and Lactobacillus spp. DNA. Paternal HFS showed increased endotoxaemia, reduced colonic gene expression of ZO1 and reduced colonic TNF-α at weaning. In the adult offspring, paternal HFS showed increased NPY, reduced serum Ghrelin, colonic pro-inflammatory cytokines, and lower faecal Bifidobacterium spp. DNA. Maternal diet showed increased hypothalamic gene expression of myeloid differentiation primary response 88 (MYD88) at weaning. The maternal HFS diet showed increased NPY and reduced faecal Bifidobacterium spp. and Lactobacillus spp. DNA in the adult offspring. The combined effect of parental diet showed increased NPY at weaning, and lower Bifidobacterium spp. and Lactobacillus spp. in the adult offspring. Maternal and paternal HFS diet seem to influence the programming of the gut-brain axis, leading to increased visceral adiposity and weight of male offspring at weaning, the effect that lasted until adulthood. [ABSTRACT FROM AUTHOR]

In addition to the amount of ingested calories, both timing of food intake and meal composition are determinants of body weight gain. However, at present, it is unknown if the inappropriate timing of diet components is responsible for body weight gain. In the present study, we therefore studied a time-dependent effect of the diet composition on energy homeostasis. Male Wistar rats were subjected to chow ad libitum (chow group) or a choice diet with saturated fat, a 30% sugar solution, chow and tap water. The choice diet was provided either with all components ad libitum (AL), with ad libitum access to chow, tap water and a 30% sugar solution, but with access to saturated fat only during the light period (LF), or with ad libitum access to chow, tap water and saturated fat, but access to a 30% sugar solution only during the light period (LS). Caloric intake and body weight gain were monitored during 31 days. Energy expenditure was measured in the third week in calorimetric cages. All rats on a choice diet showed hyperphagia and gained more body weight compared to the chow group. Within the choice diet groups, rats on the LS diet were most food efficient (i.e. gained most body weight per ingested calorie) and showed a lower respiratory exchange ratio (RER) with an anti-phasic pattern, whereas no differences in locomotor activity or heat production were found. Collectively these data indicate that the timing of the diet composition affects food efficiency, most likely due to a shifted oxidation pattern, which can predispose for obesity. Further studies are underway to assess putative mechanisms involved in this dysregulation. [ABSTRACT FROM AUTHOR]

Switching from a low-fat and high-fiber diet to a Western-style high-fat and high-sugar diet causes microbiota imbalances that underlay many pathological conditions (i.e., dysbiosis). Although the effects of dietary changes on microbiota composition and functions are well documented, their impact in gut bacterial evolution remains unexplored. We followed the emergence of mutations in Bacteroides thetaiotaomicron , a prevalent fiber-degrading microbiota member, upon colonization of the murine gut under different dietary regimens. B. thetaiotaomicron evolved rapidly in the gut and Western-style diet selected for mutations that promote degradation of mucin-derived glycans. Periodic dietary changes caused fluctuations in the frequency of such mutations and were associated with metabolic shifts, resulting in the maintenance of higher intraspecies genetic diversity compared to constant dietary regimens. These results show that dietary changes leave a genetic signature in microbiome members and suggest that B. thetaiotaomicron genetic diversity could be a biomarker for dietary differences among individuals. [Display omitted] • Bacteroides thetaiotaomicron undergoes rapid evolution upon gut colonization • Nutritional changes drive B. thetaiotaomicron fluctuating selection • Western-style diet selects for mutations favoring mucin-derived glycans degradation • Mutations in B. thetaiotaomicron reflect past host diet Changes in diet are known to affect gut metabolic and microbiota composition. Dapa et al. show that diet shapes evolution of Bacteroides thetatiotaomicron , leaving a genetic signature in this microbiota member. Alternations in diet increase intraspecies diversity, and mutations, which arise under Western-style diet, favor consumption of host mucus. [ABSTRACT FROM AUTHOR]

The comparative effects of the two commonly used antidiabetic drugs metformin and liraglutide on renal pathology and expression of connexin 45 (Cx45) and pannexin 1 (Panx1) in adult obese rats fed high-fat high-sugar diet (HFHSD) were studied. Considering recent data on the profound influence of sex on metformin and liraglutide effects, we compared the effects of both drugs between male and female animals. 44-week-old Sprague-Dawley rats were separated into 4 groups that were fed: standard diet, HFHSD, HFHSD treated with metformin (s.c., 50 mg/kg/day) and HFHSD treated with liraglutide (s.c., 0.3 mg/kg/day). Treatment with metformin or liraglutide lasted for 14 weeks. Histology and immunohistochemistry were performed to quantify renal pathological changes and Cx45 and Panx1 expression. HFHSD caused thickening of the Bowman's capsule (BC). Both metformin and liraglutide failed to ameliorate the BC thickening; metformin even worsened it. Effects on the tubulointerstitial fibrosis score, BC thickness and Cx45 and Panx1 expression were sex-dependent. We found a 50% increase in mitochondria in proximal tubules of metformin- and liraglutide-treated HFHSD-fed rats, but these effects were not dependent on the sex. This is a first study showing that the effects of metformin and liraglutide on kidney pathology in rats fed HFHSD are mostly sex-dependent and that these effects are not necessarily beneficial. Both drugs changed the Cx45 and Panx 1 expression; hence their effects could be related to amelioration of disruptions in intercellular communication. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetS) include obesity as a critical feature and is strongly associated with risk of cardiovascular disease (CVD). Insights into mechanisms involved in the pathophysiology of these clinical manifestations are essential for the development of therapeutic strategies. Thus, Western diets (WD) have been widely employed in diet-induced obesity (DIO) model. However, there are variations in fat and sugar proportions of such diets, making comparisons challenging. We aimed to assess the impact of two types of the WD on metabolic status and cardiac remodeling, to achieve a DIO model that better mimics the human pathogenesis of MetS-induced CVD. Male Wistar rats were distributed into three groups: control diet, Western diet fat (WDF), and Western diet sugar (WDS) for 41 weeks. Metabolic and inflammatory parameters and cardiac changes were characterized. WDF and WDS feeding promoted higher serum triglycerides, glucose intolerance, and insulin resistance, while just WDF presented inflammation in adipose tissue. WDF-fed rats showed increased catalase activity and malondialdehyde (MDA) and carbonyl protein levels, suggesting cardiac oxidative stress, while WDS-fed rats only raised MDA. Both WD equally elevated protein expressions involved in lipid metabolism, but only WDF downregulated the glycolysis pathway. Furthermore, the mechanical myocardial function was impaired in obese rats, being more relevant in WDF. In conclusion, both WD effectively triggered MetS features, although inflammation was detected just on the WDF-fed animals. Moreover, the WDF promoted a more pronounced functional, metabolic, and oxidative cardiac disorder, suggesting to be an adequate model for studying CVD in the scenario of MetS. [ABSTRACT FROM AUTHOR]

Obesity is recognized worldwide as a complex metabolic disorder that has reached epidemic proportions and is often associated with a high incidence of cardiovascular diseases. To study this pathology and evaluate cardiac function, several models of diet-induced obesity (DIO) have been developed. The Western diet (WD) is one of the most widely used models; however, variations in diet composition and time period of the experimental protocol make comparisons challenging. Thus, this study aimed to evaluate the effects of two different types of Western diet on cardiac remodeling in obese rats with sequential analyses during a long-term follow-up. Male Wistar rats were distributed into three groups fed with control diet (CD), Western diet fat (WDF), and Western diet sugar (WDS) for 41 weeks. The animal nutritional profile and cardiac histology were assessed at the 41st week. Cardiac structure and function were evaluated by echocardiogram at four different moments: 17, 25, 33, and 41 weeks. A noninvasive method was performed to assess systolic blood pressure at the 33rd and 41st week. The animals fed with WD (WDF and WDS) developed pronounced obesity with an average increase of 86.5% in adiposity index at the end of the experiment. WDF and WDS groups also presented hypertension. The echocardiographic data showed no structural differences among the three groups, but WDF animals presented decreased endocardial fractional shortening and ejection fraction at the 33rd and 41st week, suggesting altered systolic function. Moreover, WDF and WFS animals did not present hypertrophy and interstitial collagen accumulation in the left ventricle. In conclusion, both WD were effective in triggering severe obesity in rats; however, only the WDF induced mild cardiac dysfunction after long-term diet exposure. Further studies are needed to search for an appropriate DIO model with relevant cardiac remodeling. [ABSTRACT FROM AUTHOR]

Obesity is recognized worldwide as a complex metabolic disorder that has reached epidemic proportions and is often associated with a high incidence of cardiovascular diseases. To study this pathology and evaluate cardiac function, several models of diet-induced obesity (DIO) have been developed. The Western diet (WD) is one of the most widely used models; however, variations in diet composition and time period of the experimental protocol make comparisons challenging. Thus, this study aimed to evaluate the effects of two different types of Western diet on cardiac remodeling in obese rats with sequential analyses during a long-term follow-up. Male Wistar rats were distributed into three groups fed with control diet (CD), Western diet fat (WDF), and Western diet sugar (WDS) for 41 weeks. The animal nutritional profile and cardiac histology were assessed at the 41st week. Cardiac structure and function were evaluated by echocardiogram at four different moments: 17, 25, 33, and 41 weeks. A noninvasive method was performed to assess systolic blood pressure at the 33rd and 41st week. The animals fed with WD (WDF and WDS) developed pronounced obesity with an average increase of 86.5% in adiposity index at the end of the experiment. WDF and WDS groups also presented hypertension. The echocardiographic data showed no structural differences among the three groups, but WDF animals presented decreased endocardial fractional shortening and ejection fraction at the 33rd and 41st week, suggesting altered systolic function. Moreover, WDF and WFS animals did not present hypertrophy and interstitial collagen accumulation in the left ventricle. In conclusion, both WD were effective in triggering severe obesity in rats; however, only the WDF induced mild cardiac dysfunction after long-term diet exposure. Further studies are needed to search for an appropriate DIO model with relevant cardiac remodeling.

Diabetes and the related disease metabolic syndrome are epidemic in the United States, in part due to a shift in diet and decrease in physical exercise. PAS kinase is a sensory protein kinase associated with many of the phenotypes of these diseases, including hepatic triglyceride accumulation and metabolic dysregulation in male mice placed on a high-fat diet. Herein we provide the first characterization of the effects of western diet (high-fat high-sugar, HFHS) on Per-Arnt-Sim kinase mice (PASK−/−) and the first characterization of both male and female PASK−/− mice. Soleus muscle from the PASK−/− male mice displayed a 2-fold higher oxidative phosphorylation capacity than wild type (WT) on the normal chow diet. PASK−/− male mice were also resistant to hepatic triglyceride accumulation on the HFHS diet, displaying a 2.7-fold reduction in hepatic triglycerides compared to WT mice on the HFHS diet. These effects on male hepatic triglyceride were further explored through mass spectrometry-based lipidomics. The absence of PAS kinase was found to affect many of the 44 triglycerides analyzed, preventing hepatic triglyceride accumulation in response to the HFHS diet. In contrast, the female mice showed resistance to hepatic triglyceride accumulation on the HFHS diet regardless of genotype, suggesting the effects of PAS kinase may be masked. [ABSTRACT FROM AUTHOR]