Diet-induced Obese Rodents Research Articles

Sympathetic innervation of interscapular brown adipose tissue is not a predominant mediator of OT-elicited reductions of body weight gain and adiposity in male diet-induced obese rats.

Recent studies indicate that central administration of oxytocin (OT) reduces body weight (BW) in high fat diet-induced obese (DIO) rodents by reducing energy intake and increasing energy expenditure (EE). Previous studies in our lab have shown that administration of OT into the fourth ventricle (4V; hindbrain) elicits weight loss and stimulates interscapular brown adipose tissue temperature (TIBAT) in DIO rats. We hypothesized that OT-elicited stimulation of sympathetic nervous system (SNS) activation of IBAT contributes to its ability to activate BAT and reduce BW in DIO rats. To test this, we determined the effect of disrupting SNS activation of IBAT on OT-elicited stimulation of TIBAT and reduction of BW in DIO rats. We first confirmed that bilateral surgical SNS denervation to IBAT was successful based on having achieved ≥ 60% reduction in IBAT norepinephrine (NE) content from DIO rats. NE content was selectively reduced in IBAT by 94.7 ± 2.7, 96.8 ± 1.8 and 85.9 ± 6.1% (P<0.05) at 1, 6 and 7-weeks post-denervation, respectively, and was unchanged in liver or inguinal white adipose tissue. We then measured the impact of bilateral surgical SNS denervation to IBAT on the ability of acute 4V OT (1, 5 μg) to stimulate TIBAT in DIO rats. We found that the high dose of 4V OT (5 μg) stimulated TIBAT similarly between sham and denervated rats (P=NS) and that the effects of 4V OT to stimulate TIBAT did not require beta-3 adrenergic receptor signaling. We subsequently measured the effect of bilateral surgical denervation of IBAT on the effect of chronic 4V OT (16 nmol/day) or vehicle infusion to reduce BW, adiposity, and energy intake in DIO rats. Chronic 4V OT reduced BW gain by -7.2 ± 9.6 g and -14.1 ± 8.8 g in sham and denervated rats (P<0.05 vs vehicle treatment), respectively, and this effect was similar between groups (P=NS). These effects were associated with reductions in adiposity and energy intake (P<0.05). Collectively, these findings support the hypothesis that sympathetic innervation of IBAT is not required for central OT to increase BAT thermogenesis and reduce BW gain and adiposity in male DIO rats.

Postnatal surge of adipose-secreted leptin is a robust predictor of fat mass trajectory in mice.

The transient postnatal increase in circulating leptin levels, known as leptin surge, may increase later susceptibility to diet-induced obesity in rodents. However, the source of leptin during the surge needs to be better characterized, and the long-term effects of leptin are contradictory. Characterization of the interaction of leptin with the genetic background, sex, and other factors is required. Here, we focused on the impact of circulating leptin levels and several related variables, measured in 2- and 4-week-old (i) obesity-prone C57BL/6 (B6) and (ii) obesity-resistant A/J mice. In total, 264 mice of both sexes were used. Posttranscriptionally controlled leptin secretion from subcutaneous white adipose tissue, the largest adipose tissue depot in mice pups, was the primary determinant of plasma leptin levels. When the animals were randomly assigned standard chow or high-fat diet (HFD) between 12 - 24 weeks of age, the obesogenic effect of HFD-feeding was observed in B6 but not A/J mice. Only leptin levels at 2 weeks, i.e., close to the maximum in the postnatal leptin surge, correlated with both body weight (BW) trajectory throughout the life and adiposity of the 24-week-old mice. Leptin surge explained 13 and 7 % of the variance in BW and adiposity of B6 mice and 9 and 35 % of the variance in these parameters in A/J mice, with a minor role of sex. Our results prove the positive correlation between the leptin surge and adiposity in adulthood, reflecting the fundamental biological role of leptin. This role could be compromised in obese subjects.

Effects of systemic oxytocin and beta-3 receptor agonist (CL 316243) treatment on body weight and adiposity in male diet-induced obese rats.

Previous studies have implicated hindbrain oxytocin (OT) receptors in the control of food intake and brown adipose tissue (BAT) thermogenesis. We recently demonstrated that hindbrain [fourth ventricle (4V)] administration of oxytocin (OT) could be used as an adjunct to drugs that directly target beta-3 adrenergic receptors (β3-AR) to elicit weight loss in diet-induced obese (DIO) rodents. What remains unclear is whether systemic OT can be used as an adjunct with the β3-AR agonist, CL 316243, to increase BAT thermogenesis and elicit weight loss in DIO rats. We hypothesized that systemic OT and β3-AR agonist (CL 316243) treatment would produce an additive effect to reduce body weight and adiposity in DIO rats by decreasing food intake and stimulating BAT thermogenesis. To test this hypothesis, we determined the effects of systemic (subcutaneous) infusions of OT (50 nmol/day) or vehicle (VEH) when combined with daily systemic (intraperitoneal) injections of CL 316243 (0.5 mg/kg) or VEH on body weight, adiposity, food intake and brown adipose tissue temperature (T IBAT ). OT and CL 316243 monotherapy decreased body weight by 8.0±0.9% ( P <0.05) and 8.6±0.6% ( P <0.05), respectively, but OT in combination with CL 316243 produced more substantial weight loss (14.9±1.0%; P <0.05) compared to either treatment alone. These effects were associated with decreased adiposity, energy intake and elevated T IBAT during the treatment period. The findings from the current study suggest that the effects of systemic OT and CL 316243 to elicit weight loss are additive and appear to be driven primarily by OT-elicited changes in food intake and CL 316243-elicited increases in BAT thermogenesis.

Sympathetic innervation of interscapular brown adipose tissue is not a predominant mediator of oxytocin-elicited reductions of body weight and adiposity in male diet-induced obese mice.

Previous studies indicate that CNS administration of oxytocin (OT) reduces body weight in high fat diet-induced obese (DIO) rodents by reducing food intake and increasing energy expenditure (EE). We recently demonstrated that hindbrain (fourth ventricular [4V]) administration of OT elicits weight loss and elevates interscapular brown adipose tissue temperature (TIBAT, a surrogate measure of increased EE) in DIO mice. What remains unclear is whether OT-elicited weight loss requires increased sympathetic nervous system (SNS) outflow to IBAT. We hypothesized that OT-induced stimulation of SNS outflow to IBAT contributes to its ability to activate BAT and elicit weight loss in DIO mice. To test this hypothesis, we determined the effect of disrupting SNS activation of IBAT on the ability of 4V OT administration to increase TIBAT and elicit weight loss in DIO mice. We first determined whether bilateral surgical SNS denervation to IBAT was successful as noted by ≥ 60% reduction in IBAT norepinephrine (NE) content in DIO mice. NE content was selectively reduced in IBAT at 1-, 6- and 7-weeks post-denervation by 95.9 ± 2.0, 77.4 ± 12.7 and 93.6 ± 4.6% (P<0.05), respectively and was unchanged in inguinal white adipose tissue, pancreas or liver. We subsequently measured the effects of acute 4V OT (1, 5 µg ≈ 0.99, 4.96 nmol) on TIBAT in DIO mice following sham or bilateral surgical SNS denervation to IBAT. We found that the high dose of 4V OT (5 µg ≈ 4.96 nmol) elevated TIBAT similarly in sham mice as in denervated mice. We subsequently measured the effects of chronic 4V OT (16 nmol/day over 29 days) or vehicle infusions on body weight, adiposity and food intake in DIO mice following sham or bilateral surgical denervation of IBAT. Chronic 4V OT reduced body weight by 5.7 ± 2.23% and 6.6 ± 1.4% in sham and denervated mice (P<0.05), respectively, and this effect was similar between groups (P=NS). OT produced corresponding reductions in whole body fat mass (P<0.05). Together, these findings support the hypothesis that sympathetic innervation of IBAT is not necessary for OT-elicited increases in BAT thermogenesis and reductions of body weight and adiposity in male DIO mice.

Sympathetic innervation of interscapular brown adipose tissue is not a predominant mediator of oxytocin-elicited reductions of body weight and adiposity in male diet-induced obese mice.

Previous studies indicate that CNS administration of oxytocin (OT) reduces body weight in high fat diet-induced obese (DIO) rodents by reducing food intake and increasing energy expenditure (EE). We recently demonstrated that hindbrain (fourth ventricular [4V]) administration of OT elicits weight loss and elevates interscapular brown adipose tissue temperature (T IBAT , a surrogate measure of increased EE) in DIO mice. What remains unclear is whether OT-elicited weight loss requires increased sympathetic nervous system (SNS) outflow to IBAT. We hypothesized that OT-induced stimulation of SNS outflow to IBAT contributes to its ability to activate BAT and elicit weight loss in DIO mice. To test this hypothesis, we determined the effect of disrupting SNS activation of IBAT on the ability of 4V OT administration to increase T IBAT and elicit weight loss in DIO mice. We first determined whether bilateral surgical SNS denervation to IBAT was successful as noted by ≥ 60% reduction in IBAT norepinephrine (NE) content in DIO mice. NE content was selectively reduced in IBAT at 1-, 6- and 7-weeks post-denervation by 95.9±2.0, 77.4±12.7 and 93.6±4.6% ( P <0.05), respectively and was unchanged in inguinal white adipose tissue, pancreas or liver. We subsequently measured the effects of acute 4V OT (1, 5 µg ≈ 0.99, 4.96 nmol) on T IBAT in DIO mice following sham or bilateral surgical SNS denervation to IBAT. We found that the high dose of 4V OT (5 µg ≈ 4.96 nmol) elevated T IBAT similarly in sham mice as in denervated mice. We subsequently measured the effects of chronic 4V OT (16 nmol/day over 29 days) or vehicle infusions on body weight, adiposity and food intake in DIO mice following sham or bilateral surgical denervation of IBAT. Chronic 4V OT reduced body weight by 5.7±2.23% and 6.6±1.4% in sham and denervated mice ( P <0.05), respectively, and this effect was similar between groups ( P =NS). OT produced corresponding reductions in whole body fat mass ( P <0.05). Together, these findings support the hypothesis that sympathetic innervation of IBAT is not necessary for OT-elicited increases in BAT thermogenesis and reductions of body weight and adiposity in male DIO mice.

Anti-obesity effects of potential probiotic Lactobacillus strains isolated from Mongolian fermented dairy products in high-fat diet-induced obese rodent model.

This study aims to investigate the anti-obesity properties of lactic acid bacteria (LAB) isolated from fermented dairy products such as "Airag" and "Khoormog" in Mongolia. These traditional dairy products are widely used in Mongolia and believe in having potential probiotic, anti-diabetes, anti-cancer, and anti-tuberculosis properties and are made from unheated two-humped camel milk and mare milk, respectively. We chose three LAB strains based on their probiotic characteristics, including tolerance of gastric and bile acids. Then we checked the anti-obesity activity of probiotic strains in vivo. An animal model was evaluated in twenty male C57BL/6J mice by inducing obesity with a high-fat diet (HFD), which was divided into five groups: regular diet group (Negative control), HFD group (Positive control), HFD with Lacticaseibacillus paracasei X-1 (X-1), Lacticaseibacillus paracasei X-17 (X-17), and Limosilactobacillus fermentum BM-325 (BM-325). For six weeks, 5 × 109 colony-forming units (CFU) of bacteria were given orally to the LAB-fed groups. Fasting blood glucose (FBG), lipid profiles, organ index, and organ morphology were all measured. The probiotic strains suppressed growth in adipose cell volume, stabilized FBG, reduced liver cell degeneration, and slowed HFD-induced body weight gain. The results suggest that some strains increase general metabolism while lowering body weight.

A Combination of a Dopamine Receptor 2 Agonist and a Kappa Opioid Receptor Antagonist Synergistically Reduces Weight in Diet-Induced Obese Rodents.

As the global obesity rate increases, so does the urgency to find effective anti-obesity drugs. In the search for therapeutic targets, central nervous system (CNS) mechanisms engaged in the regulation of energy expenditure and food intake, such as the opioid and dopamine systems, are crucial. In this study, we examined the effect on body weight of two drugs: bromocriptine (BC), a D2R receptor agonist, and PF-04455242, a selective κ opioid receptor (KOR) antagonist. Using diet-induced obese (DIO) rats, we aimed to ascertain whether the administration of BC and PF-04455242, independently or in combination, could enhance body weight loss. Furthermore, the present work demonstrates that the peripheral coadministration of BC and PF-04455242 enhances the reduction of weight in DIO rats and leads to a decrease in adiposity in a food-intake-independent manner. These effects were based on heightened energy expenditure, particularly through the activation of brown adipose tissue (BAT) thermogenesis. Overall, our findings indicate that the combination of BC and PF-04455242 effectively induces body weight loss through increased energy expenditure by increasing thermogenic activity and highlight the importance of the combined use of drugs to combat obesity.

Oxytocin as an Anti-obesity Treatment.

Obesity is a growing health concern, as it increases risk for heart disease, hypertension, type 2 diabetes, cancer, COVID-19 related hospitalizations and mortality. However, current weight loss therapies are often associated with psychiatric or cardiovascular side effects or poor tolerability that limit their long-term use. The hypothalamic neuropeptide, oxytocin (OT), mediates a wide range of physiologic actions, which include reproductive behavior, formation of prosocial behaviors and control of body weight. We and others have shown that OT circumvents leptin resistance and elicits weight loss in diet-induced obese rodents and non-human primates by reducing both food intake and increasing energy expenditure (EE). Chronic intranasal OT also elicits promising effects on weight loss in obese humans. This review evaluates the potential use of OT as a therapeutic strategy to treat obesity in rodents, non-human primates, and humans, and identifies potential mechanisms that mediate this effect.

Effects of Combined Oxytocin and Beta-3 Receptor Agonist (CL 316243) Treatment on Body Weight and Adiposity in Male Diet-Induced Obese Rats.

Previous studies have indicated that oxytocin (OT) reduces body weight in diet-induced obese (DIO) rodents through reductions in energy intake and increases in energy expenditure. We recently demonstrated that hindbrain [fourth ventricular (4V)] administration of OT evokes weight loss and elevates interscapular brown adipose tissue temperature (TIBAT) in DIO rats. What remains unclear is whether OT can be used as an adjunct with other drugs that directly target beta-3 receptors in IBAT to promote BAT thermogenesis and reduce body weight in DIO rats. We hypothesized that the combined treatment of OT and the beta-3 agonist, CL 316243, would produce an additive effect to decrease body weight and adiposity in DIO rats by reducing energy intake and increasing BAT thermogenesis. We assessed the effects of 4V infusions of OT (16 nmol/day) or vehicle (VEH) in combination with daily intraperitoneal injections of CL 316243 (0.5 mg/kg) or VEH on food intake, TIBAT, body weight and body composition. OT and CL 316243 alone reduced body weight by 7.8 ± 1.3% (P < 0.05) and 9.1 ± 2.1% (P < 0.05), respectively, but the combined treatment produced more pronounced weight loss (15.5 ± 1.2%; P < 0.05) than either treatment alone. These effects were associated with decreased adiposity, adipocyte size, energy intake and increased uncoupling protein 1 (UCP-1) content in epididymal white adipose tissue (EWAT) (P < 0.05). In addition, CL 316243 alone (P < 0.05) and in combination with OT (P < 0.05) elevated TIBAT and IBAT UCP-1 content and IBAT thermogenic gene expression. These findings are consistent with the hypothesis that the combined treatment of OT and the beta-3 agonist, CL 316243, produces an additive effect to decrease body weight. The findings from the current study suggest that the effects of the combined treatment on energy intake, fat mass, adipocyte size and browning of EWAT were not additive and appear to be driven, in part, by transient changes in energy intake in response to OT or CL 316243 alone as well as CL 316243-elicited reduction of fat mass and adipocyte size and induction of browning of EWAT.

Anti-Obesity and Lipid Lowering Activity of Bauhiniastatin-1 is Mediated Through PPAR-γ/AMPK Expressions in Diet-Induced Obese Rat Model

Objective: To evaluate the therapeutic efficacy and underlying molecular mechanisms of Bauhiniastatin-1 (BSTN1) to alleviate adiposity in diet-induced obese rodent model and in 3T3-L1 cells. Methods: BSTN1 was purified and confirmed through HPLC. In-vitro experiments such as MTT assay, Oil Red-O (ORO) stain, cellular lipid content, glycerol release and RT-PCR analysis were performed in 3T3-L1 cells in the presence and absence of BSTN1. In animal experiments, rats were divided into Group-I: normal pellet diet-fed, Group-II: HFD-fed, Groups-III, IV and V: HFD-fed BSTN1 (1.25, 2.5, and 5 mg/kg.b.wt./day/rat)-treated and Group-VI: HFD-fed Orlistat-treated. The rats were fed either normal diet or high fat diet (HFD) for 18 weeks and water ad-libitum. BSTN1 was orally administered from 13th week onwards to the selected HFD-fed groups. Body composition parameters, biochemical assays, histopathology examination and western blot analysis were performed to identify the predicted targets related to obesity. Molecular docking studies threw light on the binding interactions of BSTN1 against PPAR-γ, FAS and AMPK. Results: BSTN1 at 20 μM significantly (p < 0.001) inhibited adipocyte differentiation and lipid accumulation in 3T3-L1 cells. A conspicuous down-regulation in the mRNA expression levels of PPAR-γ, FAS and SREBP1 was observed but AMPK expression remained unchanged in BSTN1 treated 3T3-L1 cells. A substantial decrease in body weight gain, fat percent, total body fat, serum and liver lipid profile (except high-density lipoprotein), glucose, insulin and insulin resistance in BSTN1 treated rats was noticed in a dose dependent manner. In BSTN1 (5 mg/kg.b.wt.)-treated groups significantly (p < 0.01) elevated plasma adiponectin level but reduced leptin level as well as fall in serum AST and ALT were noticed. Further, the disturbed structural integrity and architecture of adipose and hepatic tissues due to high fat diet feeding were considerably recovered with BSTN1 treatment. Down-regulation in the protein expression level of PPAR-γ and activation of AMPK through phosphorylation was observed in BSTN1 treated rats than the untreated. Molecular docking studies revealed strong binding interactions of BSTN1 against PPAR-γ and AMPK and thus supported the experimental results. Conclusion: Taken together, the results suggest that BSTN1 could be a promising pharmacological molecule in the treatment of obesity and dyslipidemia.

Magnesium lithospermate B supplementation improved prenatal Bisphenol A exposure-induced metabolic abnormalities in male offspring.

Obesity is closely linked with metabolic diseases, while life and prenatal exposure to endocrine-disrupting chemicals has been implicated in the development of obesity. Magnesium lithospermate B (MLB), an active compound of Salvia miltiorrhiza (Danshen), has beneficial effects on insulin resistance and metabolic abnormalities in diet-induced obese rodents. Since exposure to endocrine-disrupting chemical Bisphenol A (BPA) during pregnancy mimics the effects of high fat diet-induced alterations of glucose and lipid metabolism in adult male offspring, the effects of daily MLB supplementation for 4 weeks on metabolic abnormalities in rats weaning from prenatal BPA-exposed dams were investigated. BPA-exposed rats developed obesity and adiposity concurrent with hyperglycemia, hyperinsulinemia, insulin resistance, hypertriglyceridemia, and elevation of circulating glucagon and free fatty acids. Increased hepatic fatty acid synthesis and decreased fatty acid β-oxidation, activation of adipocytic adipogenesis, maturation, and lipogenesis, as well as reduction of muscular glucose uptake were demonstrated in BPA-exposed rats. The aforementioned alterations were improved by MLB supplementation. Additionally, MLB displayed negative effects on glucocorticoid receptor action and inflammation, and promoted lipolysis and thermogenesis in the adipose tissues. In conclusion, our findings suggest that MLB may be a potential therapeutic compound against metabolic diseases, including maternal exposure-induced metabolic abnormalities.

Sympathetic innervation of interscapular brown adipose tissue is not required for hindbrain administration of oxytocin to stimulate brown adipose tissue (BAT) thermogenesis and reduce weight gain and adiposity in DIO rats

Previous studies indicate that CNS administration of oxytocin (OT) reduces body weight in high fat diet-induced obese (DIO) rodents by reducing food intake and increasing energy expenditure (EE). We recently demonstrated that hindbrain [fourth ventricular (4V)] administration of OT elicits weight loss and elevates interscapular brown adipose tissue temperature (TIBAT; surrogate marker of increased EE) in DIO rats. What remains unclear is whether OT-elicited weight loss requires increased sympathetic nervous system (SNS) outflow to IBAT. We hypothesized that OT-induced stimulation of SNS outflow to IBAT contributes to its ability to activate BAT and elicit weight loss in DIO rats. To test this hypothesis, we determined the effect of disrupting SNS activation of IBAT on the ability of 4V OT treatment to elicit weight loss and increase TIBAT in DIO rats. We initially determined whether bilateral surgical SNS denervation to IBAT was successful as noted by ≥ 60% reduction in IBAT norepinephrine (NE) content in DIO rats. NE content was selectively reduced in IBAT at weeks 1, 6 and 7 by 95, 97 and 86% (P<0.05), respectively and was unchanged in inguinal white adipose tissue or liver. We subsequently measured the effects of chronic 4V OT (16 nmol/day) or vehicle infusions on body weight, adiposity and food intake in DIO rats following bilateral surgical (or sham) denervation of SNS innervation of IBAT. We found that chronic 4V OT reduced weight gain and fat mass in both sham and denervated rats (P<0.05) with no difference in response between groups (P=NS). These effects were attributed, in part, to reduced energy intake (P<0.05). To assess if OT-elicited changes in BAT thermogenesis require intact SNS outflow to IBAT, we examined the effects of acute 4V OT (1, 5 μg) on TIBAT in DIO rats following sham or bilateral surgical SNS denervation to IBAT. We found that the low dose (1 μg) elevated TIBAT relative to baseline in denervated rats at 0.75 (0.05<P<0.1) and 1-h post-injection (P<0.05) in denervated rats; the higher dose (5 μg) elevated TIBAT relative to baseline in both groups at 0.75, 1, 1.25, 1.5, and 1.75-h post-injection (P<0.05) with no difference in response between groups (P=NS). Together, these findings support the hypothesis that hindbrain OT treatment evokes sustained weight loss and increases BAT thermogenesis through a mechanism that does not require SNS innervation to IBAT in DIO rats.

Sympathetic innervation of interscapular brown adipose tissue is not required for hindbrain administration of oxytocin to stimulate brown adipose tissue (BAT) thermogenesis and elicit weight loss in DIO mice

Previous studies indicate that oxytocin (OT) administration reduces body weight in high fat diet-induced obese (DIO) rodents by reducing food intake and increasing energy expenditure (EE). We recently demonstrated that hindbrain (fourth ventricular; 4V) administration of OT elicits weight loss and elevates interscapular brown adipose tissue temperature (TIBAT; surrogate marker of increased EE) in DIO mice. What remains unclear is whether OT-elicited weight loss requires increased sympathetic nervous system (SNS) outflow to IBAT. We hypothesized that OT-induced stimulation of SNS outflow to IBAT contributes to its ability to activate BAT and elicit weight loss in DIO mice. To test this hypothesis, we determined the effect of disrupting SNS activation of IBAT on the ability of 4V OT administration to elicit weight loss and increase TIBAT in DIO mice. We initially determined whether bilateral surgical SNS denervation to IBAT was successful as noted by ≥ 60% reduction in IBAT norepinephrine (NE) content in DIO mice. NE content was selectively reduced in IBAT at 1, 6 and 7 weeks post-denervation by 96, 77 and 94% (P<0.05), respectively and was unchanged in inguinal white adipose tissue, pancreas or liver. We subsequently measured the effects of chronic 4V OT (16 nmol/day) or vehicle infusions on body weight, adiposity and food intake in DIO mice following sham or bilateral surgical denervation of IBAT. Chronic 4V OT reduced body weight by 5.9% and 5.4% in sham and denervated mice (P<0.05), respectively and this effect was similar between groups (P=NS). OT produced corresponding reductions in fat mass (P<0.05) that were also similar between groups (P=NS) and these effects were attributed, in part, to reduced energy intake (P<0.05). To assess if OT-elicited changes on BAT thermogenesis require intact SNS outflow to IBAT, we examined the effects of acute 4V OT (1, 5 μg) on TIBAT in DIO mice following sham or bilateral surgical SNS denervation to IBAT. We found that the high dose (5 μg) elevated TIBAT in sham mice at 0.75, 1, and 1.25-h post-injection (P<0.05) and tended to elevate TIBAT at 1.5 and 1.75-h post-injection (0.05<P<0.1). The same dose also elevated TIBAT in denervated mice at 0.75, 1, 1.25, 1.5, 2 and 3-h post-injection (P<0.05) and tended to elevate TIBAT at 4-h post-injection (0.05<P<0.1) with no difference in response between groups at 0.75, 1, and 1.25-h post-injection (P=NS). Together, these findings support the hypothesis that hindbrain OT treatment evokes sustained weight loss and increases BAT thermogenesis through a mechanism that does not require SNS innervation to IBAT in DIO mice.

Effects of Polyphenol-Rich Fruit Extracts on Diet-Induced Obesity in Rodents: Systematic Review and Meta-Analysis.

Obesity is a complex condition of high prevalence and cost to the public health system. Recent research has demonstrated the potential of natural products, such as polyphenol-rich fruit extracts, for use in the treatment of obesity. The goal of this systematic review and meta-analysis is to determine the metabolic effects of polyphenol-rich fruit extracts on diet-induced obesity (DIO) in rodents. We searched MEDLINE, EMBASE, and Web of Science databases to identify preclinical studies that assessed polyphenol-rich fruit extracts compared to placebo on DIO in rodents in December 2018. Two researchers selected the studies, extracted the data, and assessed the quality of studies. Meta-analyses of standardized mean difference (SMD) of outcomes were calculated in Stata 11, and causes of heterogeneity were assessed by meta-regression. We included 14 studies in the systematic review and 13 studies with 21 matched groups in the metaanalysis. Polyphenol-rich fruit extracts reduced the total body weight gain (SMD = -1.48; confidence interval: - 1.95, -1.01), energy intake (SMD = -0.42; -0.67, -0.17), visceral adipose tissue (SMD = -0.96; -1.25, -0.66), triglycerides (SMD = -1.00; -1.39, -0.62), cholesterol (SMD = -1.18, -1.66, -0.69), LDL- c (SMD = -1.15; -1.65, - 0.65), fasting glucose (SMD = -1.05; -1.65, -0.46), and fasting insulin (SMD = -1.40; -1.80, -1.00) when compared to vehicle. Polyphenol-rich fruit extract had positive effects on weight gain, dyslipidaemia, insulin resistance at different doses, and fruit source in male mice.

Palatable Western-style Cafeteria Diet as a Reliable Method for Modeling Diet-induced Obesity in Rodents

Palatable Western-style Cafeteria Diet as a Reliable Method for Modeling Diet-induced Obesity in Rodents

Palatable Western-style Cafeteria Diet as a Reliable Method for Modeling Diet-induced Obesity in Rodents.

Obesity is rapidly increasing in incidence in developed and developing countries and is known to induce or exacerbate many diseases.The health burden of obesity and its comorbid conditions highlight the need for better understanding of its pathogenesis, yet ethical constraints limit studies in humans. To this end externally valid models of obesity in laboratory animals are essential for the understanding of being overweight and obesity.While many species have been used to model the range of changes that accompany obesity in humans, rodents are most commonly used. Our laboratory has developed a western-style cafeteria diet that consistently leads to considerable weight gain and markers of metabolic disease in rodents. The diet exposes rodents to a variety of highly palatable foods to induce hyperphagia, modeling the modern western food environment. This diet rapidly induces weight gain and body fat accumulation in rats allowing for the study of effects of overeating and obesity. While the cafeteria diet may not provide the same control over macronutrient and micronutrient profile as purified high-fat or high-fat, high-sugar diets, the cafeteria diet typically induces a more severe metabolic phenotype than that observed with purified diets and is more in line with metabolic disturbances observed in the overweight and obese human population.

Alternate-day feeding leads to improved glucose regulation on fasting days without significant weight loss in genetically obese mice.

Alternate-day fasting (ADF) is effective for weight loss and increases insulin sensitivity in diet-induced obese rodents. However, the efficacy of ADF in genetic models of obesity has not been comprehensively studied. Mice that are deficient in leptin (ob/ob mice) are obese, diabetic, and prone to deep bouts of torpor when fasted. We tested the hypotheses that an ADF protocol in ob/ob mice would result in 1) induction of torpor on fasted days, 2) minimal body weight loss if the mice experienced torpor, and 3) no improvement in glucose control in the absence of weight loss. Female ob/ob mice and littermate controls were assigned to 1) an ad libitum regimen or 2) an ADF regimen, consisting of fasting every other day with ad libitum feeding between fasts. Over a 19-day period, littermate control mice on the ADF regimen consumed the same amount of food as littermate control mice on the ad libitum regimen, whereas the ADF ob/ob mice consumed 37% less food than ad libitum ob/ob mice. Fasting days, but not fed days, led to torpor in both genotypes. Fasting days, but not fed days, led to weight loss in both genotypes relative to ad libitum controls. Fasting days, but not fed days, produced enhanced insulin sensitivity in both genotypes and normalized circulating glucose in ob/ob mice. These data demonstrate improved glucose control on fasting days with the use of ADF in a genetic model of obesity in the face of minimal weight loss.

Vertical sleeve gastrectomy and hypertension in diet-induced obese rodents

Vertical sleeve gastrectomy and hypertension in diet-induced obese rodents

Capsaicin Targets Lipogenesis in HepG2 Cells Through AMPK Activation, AKT Inhibition and PPARs Regulation.

Obesity, a major risk factor for chronic diseases such as type 2 diabetes (T2D), represents a serious primary health problem worldwide. Dietary habits are of special interest to prevent and counteract the obesity and its associated metabolic disorders, including lipid steatosis. Capsaicin, a pungent compound of chili peppers, has been found to ameliorate diet-induced obesity in rodents and humans. The purpose of this study was to examine the effect of capsaicin on hepatic lipogenesis and to delineate the underlying signaling pathways involved, using HepG2 cells as an experimental model. Cellular neutral lipids, stained with BODIPY493/503, were quantified by flow cytometry, and the protein expression and activity were determined by immunoblotting. Capsaicin reduced basal neutral lipid content in HepG2 cells, as well that induced by troglitazone or by oleic acid. This effect of capsaicin was prevented by dorsomorphin and GW9662, pharmacological inhibitors of AMPK and PPARγ, respectively. In addition, capsaicin activated AMPK and inhibited the AKT/mTOR pathway, major regulators of hepatic lipogenesis. Furthermore, capsaicin blocked autophagy and increased PGC-1α protein. These results suggest that capsaicin behaves as an anti-lipogenic compound in HepG2 cells.

A Preventive Prebiotic Supplementation Improves the Sweet Taste Perception in Diet-Induced Obese Mice.

Orosensory perception of sweet stimulus is blunted in diet-induced obese (DIO) rodents. Although this alteration might contribute to unhealthy food choices, its origin remains to be understood. Cumulative evidence indicates that prebiotic manipulations of the gut microbiota are associated with changes in food intake by modulating hedonic and motivational drive for food reward. In the present study, we explore whether a prebiotic supplementation can also restore the taste sensation in DIO mice. The preference and licking behavior in response to various sucrose concentrations were determined using respectively two-bottle choice tests and gustometer analysis in lean and obese mice supplemented or not with 10% inulin-type fructans prebiotic (P) in a preventive manner. In DIO mice, P addition reduced the fat mass gain and energy intake, limited the gut dysbiosis and partially improved the sweet taste perception (rise both of sucrose preference and number of licks/10 s vs. non-supplemented DIO mice). No clear effect on orosensory perception of sucrose was found in the supplemented control mice. Therefore, a preventive P supplementation can partially correct the loss of sweet taste sensitivity found in DIO mice, with the efficiency of treatment being dependent from the nutritional status of mice (high fat diet vs. regular chow).