Coffee consumption prevents obesity-related comorbidities and attenuates brown adipose tissue whitening in high-fat diet-fed mice.

This study aimed to evaluate the preventive and therapeutic effects of coffee consumption on molecular changes and adipose tissue remodeling in a murine model of high-fat diet-induced obesity. Three-month-old C57BL/6 mice were initially divided into three groups, namely, control (C), high-fat (HF), and coffee prevention (HF-CP) groups, and the HF group was subdivided at the end of the 10th week into two subgroups, an HF group and a coffee treatment (HF-CT) group; thus, a total of four groups were investigated at the 14th week of the experiment. The HF-CP group had lower body mass than the HF group (-7%, P < .05) and a better distribution of adipose tissue. Both groups that received coffee (HF-CP and HF-CT) showed improved glucose metabolism compared with the HF group. Coffee consumption also attenuated adipose tissue inflammation and showed decreased macrophage infiltration and lower IL-6 levels compared with the HF group (HF-CP: -337% %, P < .05; HF-CT: -275%, P < .05). Hepatic steatosis and inflammation were attenuated in the HF-CP and HF-CT groups. The HF-CP group showed more pronounced expression of genes involved in adaptive thermogenesis and mitochondrial biogenesis (PPARγ, Prdm16, Pcg1α, ß3-adrenergic receptor, Ucp-1, and Opa-1) than the other experimental groups. Preventive coffee consumption associated with a high-fat diet ameliorates the metabolic profile related to the development of obesity and its comorbidities.

Jaboticaba (Myrciaria jaboticaba) powder consumption improves the metabolic profile and regulates gut microbiome composition in high-fat diet-fed mice.

The consumption of a high-fat diet can cause metabolic syndrome and induces host gut microbial dysbiosis and non-alcoholic fatty liver disease (NAFLD). We evaluated the effect of polyphenol-rich jaboticaba peel and seed powder (JPSP) on the gut microbial community composition and liver health in a mouse model of NAFLD. Three-month-old C57BL/6 J male mice, received either a control (C, 10% of lipids as energy, n = 16) or high-fat (HF, 50% of lipids as energy, n = 64) diet for nine weeks. The HF mice were randomly subdivided into four groups (n = 16 in each group), three of which (HF-J5, HF-J10, and HF-J15) were supplemented with dietary JPSP for four weeks (5%, 10%, and 15%, respectively). In addition to attenuating weight gain, JPSP consumption improved dyslipidemia and insulin resistance. In a dose-dependent manner, JPSP consumption ameliorated the expression of hepatic lipogenesis genes (AMPK, SREBP-1, HGMCoA, and ABCG8). The effects on the microbial community structure were determined in all JPSP-supplemented groups; however, the HF-J10 and HF-J15 diets led to a drastic depletion in the species of numerous bacterial families (Bifidobacteriaceae, Mogibacteriaceae, Christensenellaceae, Clostridiaceae, Dehalobacteriaceae, Peptococcaceae, Peptostreptococcaceae, and Ruminococcaceae) compared to the HF diet, some of which represented a reversal of increases associated with HF. The Lachnospiraceae and Enterobacteriaceae families and the Parabacteroides, Sutterella, Allobaculum, and Akkermansia genera were enriched more in the HF-J10 and HF-J15 groups than in the HF group. In conclusion, JPSP consumption improved obesity-related metabolic profiles and had a strong impact on the microbial community structure, thereby reversing NAFLD and decreasing its severity.

Antiadipogenic effects of açai seed extract on high fat diet-fed mice and 3T3-L1 adipocytes: A potential mechanism of action.

Body adiposity is an important risk factor for the development of chronic non-transmissible diseases. Studies on the process of adipogenesis have been extensively performed in vivo and in vitro models to describe the molecular and cellular bases of adipose tissue development and the effect of natural products in this process. The açai seed extract (ASE) has been evidenced as a potential regulator of body mass. In our work high-fat diet-fed mice treated with ASE (300 mg/Kg/d) (HFD-ASE) showed a lower adipose index (-32.63%, p < 0.001) than the high-fat diet-fed mice group (HFD) and the adipocytes from the HFD group were considerably enlarged (p < 0.001) compared to those in the control group (CG) and HFD-ASE group (+175% and +123%, respectively). We also evaluated the effects of ASE on the modulation of adipogenesis in 3T3-L1 cells. ASE exposure (25 and 100 µg/mL) led to a decrease of 26.6 (p < 0.05) in proliferation and also inhibited pre-adipocyte differentiation through the decreasing expression (p < 0.05) of transcription factors and adipogenic proteins such as PPARÉ£, SREBP-1, and FAS. These results show that the ASE reduce adipogenesis and suppress lipid accumulation in the in vivo model and in 3T3-L1 adipocytes and reinforce ASE as a potential strategy to modulate adipogenesis.

Morphoquantitative effects of oral ß-carotene supplementation on liver of C57BL/6 mice exposed to ethanol consumption.

Alcohol is harmful to the body, causing hepatic steatosis, alcoholic hepatitis and cirrhosis. The effects of alcohol on the liver can be offset using natural antioxidants. This study aimed to evaluate the effects of the administration of oral ß-carotene on the morphoquantitative characteristics of mice livers exposed to ethanol consumption. Forty-eight male mice were used, divided into six groups: Control (C), Low-dose alcohol (LA), Moderate-dose alcohol (MA), ß-carotene (B), Low-dose alcohol+ß-carotene (LA+B) and Moderate-dose alcohol+ß-carotene (MA+B). On day 28 the animals were euthanized and the organs were harvested. The morphoquantitative analysis, evaluation of the collagen fiber content and transmission electron microscopy were performed. A one-way ANOVA was used for statistical analysis. There were no differences between NVhep, VVhep, SVhep, VVbin, TVhep and TMhep in groups C and the MA+B (P < 0.001). The analysis of type I collagen fibers revealed that the MA+B group presented differences with groups C (P < 0.001), LA (P = 0.046) and LA+B (P = 0.009). The ultrastructural analysis for NAm, NVm, NTm, VVm, Vm, SVm and TSm did not reflect any significant differences between the groups. Our results suggest that the degree of hepatic steatosis produced by different doses of alcohol can be prevented. However, the following factors should be considered: amount of alcohol consumed, exposure time, regulatory mechanisms of alcoholic liver disease and signaling pathways involved in the ingestion of both ethanol and antioxidants.

Browning of white adipose tissue: lessons from experimental models.

Beige or brite (brown-in-white) adipocytes are present in white adipose tissue (WAT) and have a white fat-like phenotype that when stimulated acquires a brown fat-like phenotype, leading to increased thermogenesis. This phenomenon is known as browning and is more likely to occur in subcutaneous fat depots. Browning involves the expression of many transcription factors, such as PR domain containing 16 (PRDM16) and peroxisome proliferator-activated receptor (PPAR)-γ, and of uncoupling protein (UCP)-1, which is the hallmark of thermogenesis. Recent papers pointed that browning can occur in the WAT of humans, with beneficial metabolic effects. This fact indicates that these cells can be targeted to treat a range of diseases, with both pharmacological and nutritional activators. Pharmacological approaches to induce browning include the use of PPAR-α agonist, adrenergic receptor stimulation, thyroid hormone administration, irisin and FGF21 induction. Most of them act through the induction of PPAR-γ coactivator (PGC) 1-α and the consequent mitochondrial biogenesis and UCP1 induction. About the nutritional inducers, several compounds have been described with multiple mechanisms of action. Some of these activators include specific amino acids restriction, capsaicin, bile acids, Resveratrol, and retinoic acid. Besides that, some classes of lipids, as well as many plant extracts, have also been implicated in the browning of WAT. In conclusion, the discovery of browning in human WAT opens the possibility to target the adipose tissue to fight a range of diseases. Studies have arisen showing promising results and bringing new opportunities in thermogenesis and obesity control.

Combined parental obesity augments single-parent obesity effects on hypothalamus inflammation, leptin signaling (JAK/STAT), hyperphagia, and obesity in the adult mice offspring.

We aimed to evaluate the effects of maternal and/or paternal obesity on offspring body mass, leptin signaling, appetite-regulating neurotransmitters and local inflammatory markers. C57BL/6 mice received standard chow (SC, lean groups) or high-fat diet (HF, obese groups) starting from one month of age. At three months, HF mice became obese relative to SC mice. They were then mated as follows: lean mother and lean father, lean mother and obese father, obese mother and lean father, and obese mother and obese father. The offspring received the SC diet from weaning until three months of age, when they were sacrificed. In the offspring, paternal obesity did not lead to changes in the Janus kinase (JAK)/signal transducer and activation of the transcription (STAT) pathway or feeding behavior but did induce hypothalamic inflammation. On the other hand, maternal obesity resulted in increased weight gain, hyperleptinemia, decreased leptin OBRb receptor expression, JAK/STAT pathway impairment, and increased SOCS3 signaling in the offspring. In addition, maternal obesity elevated inflammatory markers and altered NPY and POMC expression in the hypothalamus. Interestingly, combined parental obesity exacerbated the deleterious outcomes compared to single-parent obesity. In conclusion, while maternal obesity is known to program metabolic changes and obesity in offspring, the current study demonstrated that obese fathers induce hypothalamus inflammation in offspring, which may contribute to the development of metabolic syndromes in adulthood.

Mice fed fish oil diet and upregulation of brown adipose tissue thermogenic markers.

PURPOSE: Fish oil (FO) elicits diverse beneficial effects. Reduction in or prevention of body mass (BM) gain in animal models may be associated with modulation of brown adipose tissue (BAT). We aimed to evaluate the effects of different high-fat diets with FO on BAT metabolism and thermogenic markers. METHODS: C57BL/6 male mice (3-month-old) were fed different diets during 8 weeks: standard-chow diet (SC 10% fat), high-fat lard diet (HF-L 50% fat), high-fat lard plus FO diet (HF-L+FO 50% fat), and high-fat FO diet (HF-FO 50% fat). We evaluated BM and performed an oral glucose tolerance test. At euthanasia, plasma was collected for leptin, and triacylglycerol measurement and interscapular BAT was dissected and stored for molecular analyses. RESULTS: HF-L group showed elevated BM; glucose intolerance associated with diminished TC10 and GLUT4 expressions; hypertriglyceridemia associated with increased CD36 and diminished CPT1 expression; elevated expression of pro-inflammatory cytokines; and reduced PPAR expression. Furthermore, these animals showed hyperleptinemia with increased expression of thermogenic markers (beta3-AR, PGC1alpha, and UCP1). Conversely, HF-L+FO and HF-FO groups showed reduced BM gain with regularization of glucose tolerance and triglyceridemia, GLUT4, TC10, CD36, CPT1, and cytokines expressions. Both groups exhibited elevated PPAR and thermogenic markers expression in a dose-dependent way. CONCLUSIONS: FO improves metabolic profile and upregulates thermogenic markers, suggesting an elevated thermogenesis that leads to reduced BM gain.

Peroxisome proliferator-activated receptors-alpha and gamma are targets to treat offspring from maternal diet-induced obesity in mice.

AIM: The aim of the present study was to evaluate whether activation of peroxisome proliferator-activated receptor (PPAR)alpha and PPARgamma by Bezafibrate (BZ) could attenuate hepatic and white adipose tissue (WAT) abnormalities in male offspring from diet-induced obese dams. MATERIALS AND METHODS: C57BL/6 female mice were fed a standard chow (SC; 10% lipids) diet or a high-fat (HF; 49% lipids) diet for 8 weeks before mating and during gestation and lactation periods. Male offspring received SC diet at weaning and were subdivided into four groups: SC, SC/BZ, HF and HF/BZ. Treatment with BZ (100 mg/Kg diet) started at 12 weeks of age and was maintained for three weeks. RESULTS: The HF diet resulted in an overweight phenotype and an increase in oral glucose intolerance and fasting glucose of dams. The HF offspring showed increased body mass, higher levels of plasmatic and hepatic triglycerides, higher levels of pro-inflammatory and lower levels of anti-inflammatory adipokines, impairment of glucose metabolism, abnormal fat pad mass distribution, higher number of larger adipocytes, hepatic steatosis, higher expression of lipogenic proteins concomitant to decreased expression of PPARalpha and carnitine palmitoyltransferase I (CPT-1) in liver, and diminished expression of PPARgamma and adiponectin in WAT. Treatment with BZ ameliorated the hepatic and WAT abnormalities generated by diet-induced maternal obesity, with improvements observed in the structural, biochemical and molecular characteristics of the animals' livers and epididymal fat. CONCLUSION: Diet-induced maternal obesity lead to alterations in metabolism, hepatic lipotoxicity and adverse liver and WAT remodeling in the offspring. Targeting PPAR with Bezafibrate has beneficial effects reducing the alterations, mainly through reduction of WAT inflammatory state through PPARgamma activation and enhanced hepatic beta-oxidation due to increased PPARalpha/PPARgamma ratio in liver.

Comparative effects of telmisartan, sitagliptin and metformin alone or in combination on obesity, insulin resistance, and liver and pancreas remodelling in C57BL/6 mice fed on a very high-fat diet.

The aim of the present study was to evaluate the effects of monotherapies and combinations of drugs on insulin sensitivity, adipose tissue morphology, and pancreatic and hepatic remodelling in C57BL/6 mice fed on a very HF (high-fat) diet. Male C57BL/6 mice were fed on an HF (60% lipids) diet or SC (standard chow; 10% lipids) diet for 10 weeks, after which time the following drug treatments began: HF-T (HF diet treated with telmisartan; 5.2 mg x kg-1 of body weight x day-1), HF-S (HF diet treated with sitagliptin; 1.08 g x kg-1 of body weight.day-1), HF-M (HF diet treated with metformin; 310.0 mg x kg-1 of body weight x day-1), HF-TM (HF diet treated with telmisartan+metformin), HF-TS (HF diet treated with telmisartan+sitagliptin) and HF-SM (HF diet treated with sitagliptin+metformin). Treated groups also had free access to the HF diet, and treatments lasted for 6 weeks. Morphometry, stereological tools, immunostaining, ELISA, Western blot analysis and electron microscopy were used. The HF diet yielded an overweight phenotype, an increase in oral glucose intolerance, hyperinsulinaemia, hypertrophied islets and adipocytes, stage 2 steatosis (>33%), and reduced liver PPAR-alpha (peroxisome-proliferator-activated receptor-alpha) and GLUT-2 (glucose transporter-2) levels, concomitant with enhanced SREBP-1 (sterol-regulatory-element-binding protein-1) expression (P<0.0001). Conversely, all drug treatments resulted in significant weight loss, a reversal of insulin resistance, islet and adipocyte hypertrophy, and alleviated hepatic steatosis. Only the HF-T and HF-TS groups had body weights similar to the SC group at the end of the experiment, and the latter treatment reversed hepatic steatosis. Increased PPAR-alpha immunostaining in parallel with higher GLUT-2 and reduced SREBP-1 expression may explain the favourable hepatic outcomes. Restoration of adipocyte size was consistent with higher adiponectin levels and lower TNF-alpha (tumour necrosis factor-alpha) levels (P<0.0001) in the drug-treated groups. In conclusion, all of the drug treatments were effective in controlling the metabolic syndrome. The best results were achieved using telmisartan and sitagliptin as monotherapies or as a dual treatment, combining partial PPAR-gamma agonism and PPAR-alpha activation in the liver with extended incretin action.

Maternal fish oil supplementation benefits programmed offspring from rat dams fed low-protein diet.

OBJECTIVE: We hypothesized that maternal fish oil supplementation would prevent the programming of offspring cardiovascular alterations. STUDY DESIGN: Forty rats were fed during the perinatal period with normal-protein (NP) diet (19%) or low-protein (LP) diet (5%) and also received daily fish oil supplement (Fo). Offspring were divided into male and female NP, NP plus Fo, and LP and LP plus Fo groups (n = 5, each) until 6 months old. Cardiac structure was examined. RESULTS: Both LP sexes had mild hypertension, but Fo supplementation minimized hypertension. The left ventricle was thicker in the LP groups and less thick in the LP plus Fo groups. The male LP had significantly fewer intramyocardial microcirculation, whereas the male LP plus Fo had 90% more microcirculation than the LP group. The LP group had significantly higher interstitial fibrosis, compared with the NP groups. CONCLUSION: Postnatal hypertension and collateral cardiovascular adverse remodeling were programmed by perinatal LP diet, whose outcomes were alleviated by maternal fish oil supplementation.