Search

In recent years, the increase in obesity in the world has led to the development of new strategies in combating obesity. In the present study, it was aimed to investigate the effect of niacin and melatonin supplements to combat obesity in rats as a model organism. Treadmill exercise was performed on rats after niacin and melatonin supplementation for 10 days. In each group, weight loss was observed at the end of the 10 days exercise. In this study, it was observed that niacin supplementation leading to weight loss in rats that had treadmill exercise when compared to the control group. In addition, it was found that the weight loss observed in melatonin+niacin supplement was higher than niacin supplement only. It was found that the weight loss observed in the group given melatonin+niacin supplement was higher than the weight loss observed in niacin supplement only. As a result, niacin and melatonin supplementation can be recommended before exercise to combat obesity.

Background and objectives A drug repurposing strategy is an approach for identifying new therapeutic uses for approved or investigational drugs. Thanks to the moderate cost of repurposing a drug compared to bringing new chemical entity to the market, drug repurposing is rapidly gaining ground. The aim of this work is to study the anti-obesity effect of disulfiram (DSF), an irreversible aldehyde dehydrogenase inhibitor approved by the Food and Drug Administration (FDA) to treat chronic alcoholism since 1951. Methods Thirty male Albino rats were randomly assigned to six groups. G1, the control group, was given a standard diet. G2, the positive control group, was given a high-fat diet (HFD). G3 was given an HFD, and DSF 50 mg/kg/day was administered orally from day one for six weeks. G4 was given an HFD, and DSF 200 mg/kg/day was administered orally from day one for six weeks. G5 was given an HFD for six weeks; then treatment started with 50 mg/kg/day DSF orally. G6 was given an HFD for six weeks; then treatment started with 200 mg/kg/day DSF orally for three weeks. The body weight, food consumption and blood glucose levels were monitored over the given time interval. Results Both doses of DSF significantly limited the body weight gain caused by an HFD for the treated animals. HF-fed rats received 50 and 200 mg/kg/day of DSF had their body weight increased by 51.93 ± 7.89% and 20.88 ± 15.05% respectively, whereas the body weight of control animals increased by 93.1 ± 20.04%. DSF also significantly decreased the body weight of obese animals. At 50 and 200 mg/kg/day of DSF, HF-fed rats lost 16.74 ± 8.61% and 23.9 ± 3.93% respectively, as their untreated counterparts had their body weight increased by 11.85 ± 3.79% after three weeks of treatment, thus restoring a body weight matching those who received a standard diet. Conclusion FDA-approved disulfiram has a strong anti-obesity effect on HFD-fed rats.

Summary Objective In shared medical appointments (SMAs), multiple patients with a similar clinical diagnosis are seen by a multidisciplinary team for interactive group sessions. Very few studies have specifically studied SMAs and weight loss in patients with obesity. This study compared weight loss outcomes and anti‐obesity medication (AOM) access between patients with obesity managed through (SMAs) versus individual appointments. Methods Retrospective study of adults seen for obesity between September 2014 and February 2017 at Cleveland Clinic Institute of Endocrinology and Metabolism. Percent weight loss from baseline was compared between two propensity score‐matched populations: patients who attended ≥1 SMA and patients managed with individual medical appointments. Results From all eligible patients identified (n=310 SMA, n=1,993 non‐SMA), 301 matched pairs were evaluated for weight loss. The SMA group (n=301) lost a mean of 4.2%, 5.2% and 3.8% of baseline weight over 6, 12 and 24 months; the non‐SMA group (n=301) lost significantly less weight (1.5%, 1.8% and 1.6%, respectively) (paired t‐test, P

The present study investigated the synergic effect of extracts of Morus alba (MA) and Aronia melanocarpa (Michx.) (AR) against high-fat diet induced obesity. Four-week-old male C57BL/6J mice were randomly divided into five groups that were fed for 14 weeks with a normal diet (ND), high-fat diet (HD), HD with M. alba 400 mg/kg body weight (MA), HD with A. melanocarpa 400 mg/kg body weight (AR), or HD with a mixture (1:1, v/v) of M. alba and A. melanocarpa (400 mg/kg) (MA + AR). Treatment with MA, AR, and MA + AR for 14 weeks reduced high fat diet-induced weight gain and improved serum lipid levels, and histological analysis revealed that MA and AR treatment markedly decreased lipid accumulation in the liver and adipocyte size in epididymal fat. Furthermore, micro-CT images showed MA + AR significantly reduced abdominal fat volume. Expression levels of genes involved in lipid anabolism, such as SREBP-1c, PPAR-γ, CEBPα, FAS, and CD36 were decreased by MA + AR treatment whereas PPAR-α, ACOX1, and CPT-1a levels were increased by MA + AR treatment. Protein expression of p-AMPK and p-ACC were increased in the MA + AR group, indicating that MA + AR ameliorated obesity by upregulating AMPK signaling. Together, our findings indicate that MA and AR exert a synergistic effect against diet-induced obesity and are promising agents for managing obesity.

Summary Objective This retrospective study aimed to evaluate the impact of anti‐obesity medication (AOM) initiation, usage and duration on weight loss in a 72‐week precision obesity programme. The type of AOM, diet and exercise plan was chosen based upon an individual's biological and psychosocial needs. The 72‐week study duration allowed for a fair investigation of the downstream impact of delayed versus early AOM initiation. Methods Participants, aged ≥18 years with body mass index ≥30 kg m−2, enrolled from 1 March 2015 to 1 April 2017, were included. Subgroups were assigned by AOM usage (users versus non‐users, early [before 8 weeks] versus delayed [after 8 weeks] AOM initiation and short [5% weight loss (P = 0.006). A higher proportion of users lost ≥15% of weight (45.1% vs. 19.0%; P < 0.001). Mean percentage reduction in weight was greater for early versus delayed starters (−17.60 ± 5.3% vs. −13.95 ± 5.5%; P = 0.024), and longer AOM usage trended towards increased weight loss. Conclusion Early initiation of AOM may enhance weight loss.

Present meta-analysis investigates the effects of phytosterols and phytostanol (PS) supplementation on anthropometric indices, using data from randomized controlled trials. We performed a systematic search in the databases: PubMed, Scopus, Cochran, and Web of Science. Weighted mean difference (WMD) with 95% confidence intervals (CIs) were presented. Overall, 79 randomized controlled trials investigated the effects of PS on anthropometric indices. Meta-analysis results did not reveal any significant effect of PS supplementation on weight (66 trials-WMD: -0.083 kg; CI [-0.233, 0.066]; I2 = 42.5%), percentage fat mass (6 trials-WMD: -0.090%; CI [-0.789, 0.610]; I2 = 0.0%), and waist circumference (WC; 5 trials-WMD: -0.039 cm; CI [-0.452, 0.374]; I2 = 0.0%). However, body mass index (BMI) significantly decreased after PS supplementation (39 trials-WMD: -0.063 kg/m2, p = 0.024, I2 = 25.1%). Subgroup analyses showed that PS supplementation in subjects with baseline BMI ≥25 and hyperlipidemic significantly decreased body weight and BMI. The overall results showed that although PS supplementation did not affect anthropometric indices (except BMI), baseline status regarding BMI and hyperlipidemia and also dose and duration could be contributing factors for favorable effects.

The incidence of obesity has been increasing dramatically worldwide over the past decades, thus requiring novel and effective therapeutic approaches. OBEX is an oral nutritional supplement composed of antioxidants with antiobesity activity. The effects of OBEX have been tested in vivo and in vitro. In vivo, OBEX reduces weight gain by decreasing adiposity gain and increasing energy expenditure in high fat diet-fed mice through the activation of thermogenesis in brown adipose tissue (BAT) independent of eating behaviors. In vitro analysis with 3T3-F442A cells revealed anti-proliferative and anti-differentiation effects of OBEX. In addition, OBEX induced a clear reduction of the lipid load in mature adipocytes obtained from 3T3-F442A cells. Overall, our findings suggest that OBEX has a protective effect against an obesogenic environment This work has been partially supported by Catalysis S.L., CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn) (Grant CB06/0003 to F.F.C.), an initiative of the Instituto de Salud Carlos III of Spain which is supported by the regional development funding program (FEDER), Xunta de Galicia (Grant GRC2014/034 to F.F.C.), Instituto de SaludCaros III (Grant PI17/01287 to F.F.C.). AGIand M.C.C. are researchers under CIBERobn contracts. A.B.C. is a researcher funded by Fundación Ramón Domínguez SI

Background: Galacto-oligosaccharides (GOS) is a commonly used as a prebiotic with a variety of metabolic benefits. Whether GOS plays a protective role in obesity is still unknown. Here we demonstrated that GOS possesses an anti-obesity activity by promoting adipose tissue browning and thermogenesis. Results: Our results showed that GOS effectively slow weight gain of diet-induced obese (DIO) rats without affecting energy intake. GOS significantly suppressed the hypertrophy and hyperplasia of white adipose tissue (WAT), as well as markedly lessened the ratio of fat pad to fat body. Consistently, GOS significantly improved serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels, which indicated an appropriate weight loss activity of GOS. Interestingly, GOS also significantly increased the expression levels of browning proteins (UCP1, PPARγ, PGC1α and PRMD16) both in the WAT and brown adipose tissue (BAT). We further found that GOS markedly increased the expression levels of LXRα, PPARα, LDLR and CYP7A1 proteins in the liver of obese rats. Conclusions: Taken together, we concluded that GOS inhibits obesity by accelerating the browning of white fat cells and the thermogenesis of brown fat cells, moreover GOS improves host lipid homeostasis by promoting cholesterol catabolism.

BackgroundBilateral ovariectomy is an experimental model used to analyze the conditions of menopause and develop strategies for alleviation of the deleterious effects during estrogen deficiency. Brown and beige adipocytes exert thermogenesis capacities and are promising therapeutic strategy for obesity. This study aims to investigate the adipose tissue browning potentials of antioxidant α-lipoic acid (ALA) and underlying mechanisms involved in ovariectomized (Ovx) rats.Methods:Eight weeks old female Wistar rats were randomly divided into Sham or Ovx groups. The Ovx rats were subjected to bilateral ovariectomy and administered with ALA 200 or ALA 300 mg/kg/day (gavage) for 8 weeks. Results:Ovx group significantly increased boy weight (BW) and fat pad mass as compared to Sham group, while ALA supplementation reversed these changes. Lipid profiles including serum triglycerides (TG), total (TC) and low-density lipoprotein cholesterol (LDL-C) levels were significantly elevated in the Ovx group, whereas the ALA treatment showed a significant decrease in these levels. Furthermore, high density lipoprotein cholesterol (HDL-C) and myokine irisin secretion were increased by ALA as well. Morphology results showed ALA treatment reduced Ovx-induced adipocyte hypertrophy and enhanced UCP1 expression by immunohistochemical staining in inguinal WAT. Protein expression of brown fat-specific markers UCP1, PRDM16 and CIDEA was markedly reduced in Ovx rats, whereas ALA treatment reversed these changes. ALA significantly increased liver kinase B1 (LKB1) and phosphorylation of AMP-activated protein kinase (AMPK) and the downstream acetyl-CoA carboxylase (ACC) that were decreased by Ovx, suggesting the browning effects were mediated by AMPK signaling. Conclusions:ALA ameliorates obesity caused by hormone deprivation in menopause via conversion of white to beige adipocytes concomitant with the activation of AMPK signaling.

Over the past few decades, several anti-obesity medications have demonstrated an association with adverse cardiovascular outcomes, leading to their market withdrawal. This has caused researchers to investigate the cardiovascular safety of such medications in cardiovascular outcome trials. However, the data from these trials are limited, and their outcomes are not promising. Therefore, the aim of this review is to provide an overview of the current and past Food and Drug Administration-approved medications for weight loss, including novel diabetes medications (glucagon-like peptide 1 receptor agonists and sodium-glucose co-transporter-2 inhibitors) and non-diabetes medications, and to highlight the current designs of cardiovascular outcome trials and their importance in the evaluation of the overall safety concerns associated with these anti-obesity medications. The limitations of the trials and opportunities for improvement were also evaluated. Finally, we also briefly describe cardiovascular safety and risks in this review.

Design and rationale: Obesity results from energy intake exceeding energy expenditure (EE) over a prolonged period. Many anti-obesity drugs are designed to decrease energy intake. However, their potential impact on EE is not well documented. We designed a placebo-controlled, double-blind, randomized cross-over study to determine the acute effects of several FDA-approved anti-obesity drugs on basal metabolic rate (BMR) under well-controlled conditions. Protocol and inclusion criteria: This ongoing study is limited to healthy males of all ethnicities aged 18–35 years with a BMI of 18.5 to 25.0 kg/m2. Following an overnight stay in the Metabolic Clinical Research Unit, fasting subjects were measured from 8:00am to 12:00pm in a whole-room indirect calorimeter, which was maintained at a thermoneutral temperature (26.7±0.9°C) to prevent non-shivering thermogenesis. The six treatments include placebo, caffeine as the positive control (300 mg), phentermine (37.5 mg), topiramate (200 mg), Qsymia (phentermine 15 mg / topiramate 92 mg), and naltrexone (100 mg), with a 1-week outpatient washout period after each treatment. Drug-naïve subjects received a single dose of each drug to minimize potential metabolic adaptations that may occur with weight-loss or chronic use. The prespecified primary outcome was a ≥5% increase in BMR vs. placebo for each drug. This difference can be detected for 16 subjects with 0.83 power at α=0.05 allowing for ≤25% dropout. Secondary outcomes include respiratory quotient (RQ), heart rate (HR), mean arterial pressure (MAP), and self-reported hunger. Preliminary data: To date, 7 subjects were recruited and 6 have completed the study (26.1±4.3 years, BMI 23.1±1.4 kg/m2, body fat percentage 18.4±4.1%). Interim analysis using paired t-tests shows, compared to placebo, caffeine trended towards increasing EE (1.17±0.07 vs. 1.27±0.12 kcal/min; p=0.07) and increased MAP by 5.5±4.2% (88±2 vs. 93±4; p Summary and future directions: Anti-obesity drugs may increase energy expenditure by upregulating sympathetic nervous system activity. Combined with appetite suppression, the impact on energy balance can lead to weight loss. We aim to complete our study to determine whether these drugs can acutely increase EE with minimal cardiovascular side-effects and compare our findings with long-term interventions.

Background: Obesity is excess body weight for a given height. It is a worldwide pandemic associated with increased morbidity/mortality and high cost for the society. The prevalence of obesity has doubled in more than 70 countries since 1980. The prevalence of obesity in the United States of America (USA) is near 40% and its annual medical cost is around $200 billion. Management of obesity requires multidisciplinary approaches. Available options for weight reduction include diet, food supplement, exercise, behavior change, drug, medical device, gut microbiome manipulation, and surgery. In the USA, only 2% of subjects with obesity receive anti-obesity drugs. Properties and Mechanisms of Action: Anti-obesity medical devices represent a heterogenous family in terms of regulation, presentation, usage/administration, mechanism of action, effectiveness, safety, availability, and cost. Unlike anti-obesity drugs that act chemically through specific receptors, anti-obesity medical devices act rather mechanically. They do not have systemic absorption, specific metabolism, or receptors, and, therefore, have no side effects related to the impact on different organs through the bloodstream. Anti-obesity medical devices can cause weight loss through different mechanisms. They can cause a decrease in food intake at the level of oral cavity (by limiting the bite size) or stomach (by reducing the available stomach volume), or can cause a decrease in the amount of available/absorbed nutrient at the level of stomach (by removing part of the gastric contents) or intestine (by bypassing part of the intestine). In the USA, the Center for Devices and Radiological Health (CDRH) of the Food and Drug Administration is approving/clearing the anti-obesity medical devices. Based on the expected weight loss, CDRH categorizes medical devices as weight-loss devices (“more” weight loss) or weight-management devices (“less” weight loss). The weight-loss devices include gastric band devices, gastric space-occupying devices, and gastric emptying devices. The weight-management devices include oral removable palatal space-occupying devices and ingested transient gastric space-occupying devices. Anti-obesity medical devices should be used in conjunction with healthy lifestyle including diet and exercise. The degree of weight loss, the side effects, and the cost of anti-obesity medical devices vary considerably by the type of medical device. Conclusion: Anti-obesity medical devices are an option for subjects who have not responded to more conservative treatments (lifestyle, drugs) but who want an alternative to more aggressive interventions (bariatric surgery). Given the large market size of obesity treatment and the current level of undertreatment with anti-obesity drugs, anti-obesity medical devices can play a major role in the management of obesity.

In this work, the effect of the intake of a low-fat diet supplemented with a fruit puree (guava-strawberry, guava-blackberry, guava-soursop or guava-passion fruit) by obese rats on reduction of body weight, lipid profile, and liver enzyme activity was evaluated. The rats (n=6 for each treatment) were induced to obesity with a high-fat diet for 4 weeks, then they were fed with a low-fat diet plus a fruit puree for 4 weeks. Healthy rats and obese rats fed with standard diet as controls were considered. The additional consumption of fruit purees was associated with a reduction in body weight (16-24%), a control in the metabolism of plasma lipids decreasing the levels of total cholesterol (59-68%) and triacylglycerols (61-82%). We found a significant reduction in inflammation markers and liver damage; enzyme activity (alanine aminotransaminase, aspartate aminotransferase, γ-glutamyl transferase and alkaline phosphatase) decreased, and a notable improvement in liver morphology was observed. The consumption of fruit purees by obese individuals could contribute to the control of and improvement in the complications of obesity caused by alterations in lipoproteins.

Obesity is a global disorder with multifactorial causes. The liver plays a vital role in fat metabolism. Disorder of hepatic fat metabolism is associated with obesity and causes fatty liver. High fat diet intake (HFD) to mice causes the development of dietinduced obesity (DIO). The study aimed to detect the effects of anti-obesity drugs (sulforaphane; SFN and leptin) on hepatic gene expression of fat metabolism in mice that were fed HFD during an early time of DIO. Twenty wild types (WT) CD1 male mice aged ten weeks were fed a high fat diet. The mice were treated with vehicle; Veh (control group), and SFN, then each group is treated with leptin or saline. Four groups of treatment were: control group (vehicle + saline), Group 2 (vehicle + leptin), group 3 (SFN + saline), and group 4 (SFN + leptin). Body weight and food intake were monitored during the treatment period. Following the treatments of leptin 24 hour, fasting blood samples and liver tissue was collected, and Total RNA was extracted then used to assess the gene expression of 84 genes involved in hepatic fat metabolism using RT-PCR profiler array technique. Leptin treatment upregulated fatty acid betaoxidation (Acsbg2, Acsm4) and fatty acyl-CoA biosynthesis (Acot6, Acsl6), and downregulated is fatty acid transport (Slc27a2). SFN upregulated acylCoA hydrolase (Acot3) and long chain fatty acid activation for lipids synthesis and beta oxidation (Acsl1). Leptin + SFN upregulated fatty acid beta oxidation (Acad11, Acam) and acyl-CoA hydrolase (Acot3, Acot7), and downregulated fatty acid elongation (Acot2). As a result, treatment of both SFN and leptin has more profound effects on ameliorating pathways involved in hepatic lipogenesis and TG accumulation and lipid profile of TG and TC than other types of intervention. We conclude that early intervention of obesity pa could ameliorate the metabolic changes of fat metabolism in liver as observed in WT mice on HFD in response to anti-obesity treatment.

Porous colloids have been shown to exert unique bioactivities for mediating lipid (fat) metabolism and thereby offer significant potential as anti-obesity therapies. In this study, we compare the capacity for two classes of colloids, that is, smectite clays (Laponite XLG, LAP; montmorillonite, MMT) and mesoporous silica (SBA-15 ordered silica; MPS), to impede intestinal lipid hydrolysis and provoke lipid and carbohydrate excretion through adsorption within their particle matrices. A two-stage in vitro gastrointestinal lipolysis model revealed the capacity for both smectite clays and MPS to inhibit the rate and extent of lipase-mediated digestion under simulated fed state conditions. Each system adsorbed more than its own weight of organic media (i.e., lipid and carbohydrates) after 60 min lipolysis, with MMT adsorbing >10% of all available organics through the indiscriminate adsorption of fatty acids and glycerides. When co-administered with a high-fat diet (HFD) to Sprague-Dawley rats, treatment with MMT and MPS significantly reduced normalized rodent weight gain compared to a negative control, validating their potential to restrict energy intake and serve as anti-obesity therapies. However, in vitro-in vivo correlations revealed poor associations between in vitro digestion parameters and normalized weight gain, indicating that additional/alternate anti-obesity mechanisms may exist in vivo, while also highlighting the need for improved in vitro assessment methodologies. Despite this, the current findings emphasize the potential for porous colloids to restrict weight gain and promote anti-obesity effects to subjects exposed to a HFD and should therefore drive the development of next-generation food-grade biomaterials for the treatment and prevention of obesity. Refereed/Peer-reviewed

"Diabesity" is the term to illustrate the interdependent relationship between obesity and diabetes. About 80% of the diabetic patients are diagnosed with obesity. Diabesity can be prevented by dietary interventions, especially by incorporating sufficient amount of resistant starch (RS). In the past few decades, RS has inspired the researchers due to its various health benefits. Differing from digestible starch, RS remains undigested in the small intestine, but in the large intestine, it is subjected to fermentation. This review intends to encapsulate the current information related to the dietary RS on diabetes and obesity. RS attenuate hyperglycemic, hyperinsulinemic and hyperlipidemic response in various subjects by restricting gluconeogenesis, bolstering glycogenesis, maintaining glucose and lipid homeostasis and ameliorating pancreatic dysfunction. Various food products were fortified with RS to enhance its dietary intake and were found to exhibit positive impact on human and animal models. This review identified and summarized the research gaps in the available literature.

Obesity is associated with the risk of developing several severe diseases, such as metabolic disorder, diabetes, and heart diseases. Despite wide investigation and trials, a noninvasive obesity therapy is still an important medical unmet need, targeting the abnormal adipose tissue. Here, we developed hyaluronate-hollow gold nanosphere-adipocyte-targeting peptide (HA-HAuNS-ATP) conjugates for the photothermal ablation of adipose tissues. The HA-HAuNS-ATP conjugate could be noninvasively delivered into the skin and effectively target to adipocytes in the subcutaneous. With near-infrared laser illumination, HA-HAuNS-ATP conjugate enabled highly effective photothermal ablation of adipose tissues in C57BL/6 obesity mice. The photoacoustic imaging confirmed the successful transdermal delivery and the photothermal lipolysis of HA-HAuNS-ATP conjugate. Taken together, the transdermal HA-HAuNS-ATP conjugate might have a great potential for noninvasive photothermal lipolysis.

Could the FDA’s supplemental approval of Novo Nordisk’s semaglutide for weight loss be a turning point for anti-obesity drugs? Could the FDA’s supplemental approval of Novo Nordisk’s semaglutide for weight loss be a turning point for anti-obesity drugs?

The main purpose of this study was to compare the benefits of SSJ supplementation in obese rats with those achieved only by switching the alimentary regimen from high-fat (HFD) to the regular one (RD) in liver, ileum and prostate. Furthermore, changings in caecal chime microbiota were investigated. SSJ was administered to rats in combination with a RD (HFD-RD + SSJ). The switch from HFD to RD led to a weight loss of almost 9.8 g, and the total cholesterol was found to be significantly lower. In the HFD-RD + SSJ group, all values were improved compared with the HFD control, and the weight decrement was higher (-23.29 g) with respect to HFD-RD. HFD led to a widespread increment of oxidative stress (OS) markers in liver, ileum and prostate. SSJ has shown to improve the results achieved by the suspension of HFD and it has proven effective wherever the only switch in diet regimen failed.

The angiotensin II (ANG II)-ANG II type 1 receptor (AT1R) axis is a key player in the pathophysiology of obesity. Angiotensin-converting enzyme 2 (ACE2) counteracts the ANG II/AT1R axis via converting ANG II to angiotensin 1–7 (Ang 1–7), which is known to have an anti-obesity effect. In this study, we hypothesized that ACE2 exerts a strong anti-obesity effect by increasing Ang 1–7 levels. We injected intraperitoneally recombinant human ACE2 (rhACE2, 2.0 mg·kg−1·day−1) for 28 days to high-fat diet (HFD)-induced obesity mice. rhACE2 treatment decreased body weight and improved glucose metabolism. Furthermore, rhACE2 increased oxygen consumption and upregulated thermogenesis in HFD-fed mice. In the rhACE2 treatment group, brown adipose tissue (BAT) mass increased, accompanied with ameliorated insulin signaling and increased protein levels of uncoupling protein-1 (UCP-1) and PRD1-BF1-RIZ1 homologous domain containing 16. Importantly, subcutaneous white adipose tissue (sWAT) mass decreased, concomitant with browning, which was established by the increase of UCP-1 expression. The browning is the result of increased H3K27 acetylation via the downregulation of histone deacetylase 3 and increased H3K9 acetylation via upregulation of GCN5 and P300/CBP-associated factor. These results suggest that rhACE2 exerts anti-obesity effects by stimulating BAT and inducing browning in sWAT. ACE2 and the Ang 1–7 axis represent a potential therapeutic approach to prevent the development of obesity.