GABAergic leptin receptor-expressing neurons in the dorsomedial hypothalamus project to brown adipose tissue-related neurons in the paraventricular nucleus of mice.

Brown adipose tissue (BAT) contributes to energy homeostasis via nonshivering thermogenesis. The BAT is densely innervated by the sympathetic nervous system (SNS) and activity of pre-autonomic neurons modulates the sympathetic outflow. Leptin, an adipocyte hormone, alters energy homeostasis and thermogenesis of BAT via several neuronal circuits; however, the cellular effects of leptin on interscapular BAT (iBAT)-related neurons in the hypothalamus remain to be determined. In this study, we used pseudorabies virus (PRV) to identify iBAT-related neurons in the paraventricular nucleus (PVN) of the hypothalamus and test the hypothesis that iBAT-related PVN neurons are modulated by leptin. Inoculation of iBAT with PRV in leptin receptor reporter mice (Lepr:EGFP) demonstrated that a population of iBAT-related PVN neurons expresses Lepr receptors. Our electrophysiological findings revealed that leptin application caused hyperpolarization in some of iBAT-related PVN neurons. Bath application of leptin also modulated excitatory and inhibitory neurotransmission to most of iBAT-related PVN neurons. Using channel rhodopsin assisted circuit mapping we found that GABAergic and glutamatergic Lepr-expressing neurons in the dorsomedial hypothalamus/dorsal hypothalamic area (dDMH/DHA) project to PVN neurons; however, connected iBAT-related PVN neurons receive exclusively inhibitory signals from Lepr-expressing dDMH/DHA neurons.

Neural circuits mediating circulating interleukin-1ß-evoked fever in the absence of prostaglandin E2 production.

Infectious diseases and inflammatory conditions recruit the immune system to mount an appropriate acute response that includes the production of cytokines. Cytokines evoke neurally-mediated responses to fight pathogens, such as the recruitment of thermoeffectors, thereby increasing body temperature and leading to fever. Studies suggest that the cytokine interleukin-1ß (IL-1ß) depends upon cyclooxygenase (COX)-mediated prostaglandin E2 production for the induction of neural mechanisms to elicit fever. However, COX inhibitors do not eliminate IL-1ß-induced fever, thus suggesting that COX-dependent and COX-independent mechanisms are recruited for increasing body temperature after peripheral administration of IL-1ß. In the present study, we aimed to build a foundation for the neural circuit(s) controlling COX-independent, inflammatory fever by determining the involvement of brain areas that are critical for controlling the sympathetic outflow to brown adipose tissue (BAT) and the cutaneous vasculature. In anesthetized rats, pretreatment with indomethacin, a non-selective COX inhibitor, did not prevent BAT thermogenesis or cutaneous vasoconstriction (CVC) induced by intravenous IL-1ß (2 µg/kg). BAT and cutaneous vasculature sympathetic premotor neurons in the rostral raphe pallidus area (rRPa) are required for IL-1ß-evoked BAT thermogenesis and CVC, with or without pretreatment with indomethacin. Additionally, activation of glutamate receptors in the dorsomedial hypothalamus (DMH) is required for COX-independent, IL-1ß-induced BAT thermogenesis. Therefore, our data suggests that COX-independent mechanisms elicit activation of neurons within the DMH and rRPa, which is sufficient to trigger and mount inflammatory fever. These data provide a foundation for elucidating the brain circuits responsible for COX-independent, IL-1ß-elicited fevers.

PET/MRI-evaluated brown adipose tissue activity may be related to dietary MUFA and omega-6 fatty acids intake.

An investigation of new ways to activate brown adipose tissue (BAT) is highly valuable, as it is a possible tool for obesity prevention and treatment. The aim of our study was to evaluate the relationships between dietary intake and BAT activity. The study group comprised 28 healthy non-smoking males aged 21-42 years. All volunteers underwent a physical examination and 75-g OGTT and completed 3-day food intake diaries to evaluate macronutrients and fatty acid intake. Body composition measurements were assessed using DXA scanning. An FDG-18 PET/MR was performed to visualize BAT activity. Brown adipose tissue was detected in 18 subjects (67% normal-weight individuals and 33% overweight/obese). The presence of BAT corresponded with a lower visceral adipose tissue (VAT) content (p = 0.04, after adjustment for age, daily kcal intake, and DXA Lean mass). We noted significantly lower omega-6 fatty acids (p = 0.03) and MUFA (p = 0.02) intake in subjects with detected BAT activity after adjustment for age, daily average kcal intake, and DXA Lean mass, whereas omega-3 fatty acids intake was comparable between the two groups. BAT presence was positively associated with the concentration of serum IL-6 (p = 0.01) during cold exposure. Our results show that BAT activity may be related to daily omega-6 fatty acids intake.

Tangeretin prevents obesity by modulating systemic inflammation, fat browning, and gut microbiota in high-fat diet-induced obese C57BL/6 mice.

Obesity and associated comorbidities are closely linked to gut microbiota dysbiosis, energy balance, and chronic inflammation. Tangeretin, a key citrus polymethoxylated flavone (PMF), is abundant in citrus fruits and has preventative and therapeutic effects for numerous diseases. The current study investigated the effects and possible mechanisms of tangeretin supplementation in preventing obesity in high-fat diet (HFD)-fed mice. Treatment of HFD-fed mice with tangeretin potently ameliorated HFD-induced body weight, liver steatosis, glucose intolerance, and insulin resistance. Tangeretin mitigated systemic chronic inflammation by reducing metabolic endotoxemia and inflammation-related gene expression in HFD-fed mice. An increased number of small brown adipocytes possessing multilocular and cytoplasmic lipid droplets and upregulation of thermogenic gene expression were observed after tangeretin treatment. 16S rRNA amplicon sequencing indicated that tangeretin markedly altered the gut microbiota composition (richness and diversity) and reversed 16 operational taxonomic units (OTUs) back to levels seen in mice consuming a normal chow diet (NCD). Notably, tangeretin decreased the ratio of Firmicutes-to-Bacteroidetes and greatly enriched Bacteroides and Lactobacillus. Overall, our results suggest that long-term supplementation with citrus tangeretin ameliorates the phenotype of obesity by improving adipose thermogenesis and reducing systemic inflammation and gut microbiota dysbiosis, which provides a good basis for studying the mechanism of tangeretin's beneficial effects.

Dietary succinate supplementation to maternal mice improves fetal brown adipose tissue development and thermogenesis of female offspring.

Succinic acid widely exists in foods and is used as a food additive. Succinate not only serves as an energy substrate, but also induces protein succinylation. Histone succinylation activates gene transcription. The brown adipose tissue (BAT) is critical for prevention of obesity and metabolic dysfunction, and the fetal stage is pivotal for BAT development. Up to now, the role of maternal succinate supplementation on fetal BAT development and offspring BAT function remains unexamined. To test, female C57BL/6J mice (2-month-old) were separated into 2 groups, received with or without 0.5% succinic acid in drinking water during gestation and lactation. After weaning, female offspring were challenged with high fat diet (HFD) for 12 weeks. Newborn, female weanling, and HFD female offspring mice were analyzed. For neonatal and weaning mice, the BAT weight relative to the whole body weight was significantly increased in the succinate group. The expression of PGC-1α, a key transcription co-activator promoting mitochondrial biogenesis, was elevated in BAT of female neonatal and offspring born to succinate-fed dams. Consistently, maternal succinate supplementation enhanced thermogenesis and the expression of thermogenic genes in offspring BAT. Additionally, maternal succinate supplementation protected female offspring against HFD-induced obesity. Furthermore, in C3H10T1/2 cells, succinate supplementation promoted PGC-1α expression and brown adipogenesis. Mechanistically, succinate supplementation increased permissive histone succinylation and H3K4me3 modification in the Ppargc1a promoter, which correlated with the higher expression of Ppargc1a. In conclusion, maternal succinate supplementation during pregnancy and lactation enhanced fetal BAT development and offspring BAT thermogenesis, which prevented HFD-induced obesity and metabolism dysfunction in offspring.

A Novel Multi-Ingredient Supplement Activates a Browning Program in White Adipose Tissue and Mitigates Weight Gain in High-Fat Diet-Fed Mice.

We investigated the effects of a novel multi-ingredient supplement comprised of polyphenol antioxidants and compounds known to facilitate mitochondrial function and metabolic enhancement (ME) in a mouse model of obesity. In this study, 6-week-old male C57/BL6J mice were placed on a high-fat diet (HFD; ~60% fat) for 6 weeks, with subsequent allocation into experimentalgroups for 4 weeks: HFD control, HFD + ME10 (10 components), HFD + ME7 (7 components), HFD + ME10 + EX, HFD + EX (where '+EX' animals exercised 3 days/week), and chow-fed control. After the intervention, HFD control animals had significantly greater body weight and fat mass. Despite the continuation of HFD, animals supplemented with multi-ingredient ME or who performed exercise training showed an attenuation of fat mass and preservation of lean body mass, which was further enhanced when combined (ME+EX). ME supplementation stimulated the upregulation of white and brown adipose tissue mRNA transcripts associated with mitochondrial biogenesis, browning, fatty acid transport, and fat metabolism. In WAT depots, this was mirrored by mitochodrial oxidative phosphorylation (OXPHOS) protein expression, and increased in vivo fat oxidation measured via CLAMS. ME supplementation also decreased systemic and local inflammation markers. Herein, we demonstrated that novel multi-ingredient nutritional supplements induced significant fat loss independent of physical activity while preserving muscle mass in obese mice. Mechanistically, these MEs appear to act by inducing a browning program in white adipose tissue and decreasing other pathophysiological impairments associated with obesity, including mitochondrial respiration alterations induced by HFD.

Inhibitory effects of fermented Ougan (Citrus reticulata cv. Suavissima) juice on high-fat diet-induced obesity associated with white adipose tissue browning and gut microbiota modulation in mice.

In this study, Ougan juice (OJ) and lactic acid bacteria fermented Ougan juice (FOJ) were investigated individually for their capability of preventing obesity in high-fat diet (HFD)-fed C57BL/6J mice. After being administered with OJ or FOJ for 10 weeks, the body weight gain, hyperlipidemia, and gut microbiota dysbiosis of HFD-fed mice were examined. The results showed that OJ or FOJ supplementation inhibited weight gain, lowered fat accumulation, reduced liver steatosis, improved glucose homeostasis and insulin sensitivity, increased brown adipose tissue (BAT) activity, and promoted white adipose tissue (WAT) browning. Both OJ and FOJ additions increased the diversity of gut microbiota. OJ reduced the relative abundance of phylum Erysipelatoclostridiaceae and genus Erysipelatoclostridium and remarkably increased SCFA-producing bacteria Blautia, while FOJ reduced the ratio of Firmicutes to Bacteroidetes and enhanced the relative abundance of family Lactobacillaceae. Spearman's correlation analysis revealed that Akkermansia, Dubosiella, and Muribaculaceae were significantly negatively correlated with obesity-related indexes. In general, FOJ exhibited a better inhibitory effect on obesity than OJ, and the possible inhibitory mechanism lies in promoting WAT browning and increasing intestinal probiotics. This study provides the guidance for developing fermented Ougan juice as an obesity-inhibiting functional food.

Brown Adipose Tissue: New Challenges for Prevention of Childhood Obesity. A Narrative Review.

Pediatric obesity remains a challenge in modern society. Recently, research has focused on the role of the brown adipose tissue (BAT) as a potential target of intervention. In this review, we revised preclinical and clinical works on factors that may promote BAT or browning of white adipose tissue (WAT) from fetal age to adolescence. Maternal lifestyle, type of breastfeeding and healthy microbiota can affect the thermogenic activity of BAT. Environmental factors such as exposure to cold or physical activity also play a role in promoting and activating BAT. Most of the evidence is preclinical, although in clinic there is some evidence on the role of omega-3 PUFAs (EPA and DHA) supplementation on BAT activation. Clinical studies are needed to dissect the early factors and their modulation to allow proper BAT development and functions and to prevent onset of childhood obesity.

Nicotinamide Protects Against Diet-Induced Body Weight Gain, Increases Energy Expenditure, and Induces White Adipose Tissue Beiging.

SCOPE: Interventions that boost NAD+ availability are of potential therapeutic interest for obesity treatment. The potential of nicotinamide (NAM), the amide form of vitamin B3 and a physiological precursor of nicotinamide adenine dinucleotide (NAD)+ , in preventing weight gain has not previously been studied in vivo. Other NAD+ precursors have been shown to decrease weight gain; however, their impact on adipose tissue is not addressed. METHODS AND RESULTS: Two doses of NAM (high dose: 1% and low dose: 0.25%) are given by drinking water to C57BL/6J male mice, starting at the same time as the high-fat diet feeding. NAM supplementation protects against diet-induced obesity by augmenting global body energy expenditure in C57BL/6J male mice. The manipulation markedly alters adipose morphology and metabolism, particularly in inguinal (i) white adipose tissue (iWAT). An increased number of brown and beige adipocyte clusters, protein abundance of uncoupling protein 1 (UCP1), mitochondrial activity, adipose NAD+ , and phosphorylated AMP-activated protein kinase (P-AMPK) levels are observed in the iWAT of treated mice. Notably, a significant improvement in hepatic steatosis, inflammation, and glucose tolerance is also observed in NAM high-dose treated mice. CONCLUSION: NAM influences whole-body energy expenditure by driving changes in the adipose phenotype. Thus, NAM is an attractive potential treatment for preventing obesity and associated complications.

Nicotinamide Riboside Enhances In Vitro Beta-adrenergic Brown Adipose Tissue Activity in Humans.

CONTEXT: Elevating nicotinamide adenine dinucleotide (NAD+) levels systemically improves metabolic health, which can be accomplished via nicotinamide riboside (NR). Previously, it was demonstrated that NR supplementation in high-fat-diet (HFD)-fed mice decreased weight gain, normalized glucose metabolism, and enhanced cold tolerance. OBJECTIVE: Because brown adipose tissue (BAT) is a major source of thermogenesis, we hypothesize that NR stimulates BAT in mice and humans. DESIGN AND INTERVENTION: HFD-fed C56BL/6J mice were supplemented with 400 mg/kg/day NR for 4 weeks and subsequently exposed to cold. In vitro primary adipocytes derived from human BAT biopsies were pretreated with 50 µM or 500 µM NR before measuring mitochondrial uncoupling. Human volunteers (45-65 years; body mass index, 27-35 kg/m2) were supplemented with 1000 mg/day NR for 6 weeks to determine whether BAT activity increased, as measured by [18F]FDG uptake via positron emission tomography-computed tomography (randomized, double blinded, placebo-controlled, crossover study with NR supplementation). RESULTS: NR supplementation in HFD-fed mice decreased adipocyte cell size in BAT. Cold exposure further decreased adipocyte cell size on top of that achieved by NR alone independent of ex vivo lipolysis. In adipocytes derived from human BAT, NR enhanced in vitro norepinephrine-stimulated mitochondrial uncoupling. However, NR supplementation in human volunteers did not alter BAT activity or cold-induced thermogenesis. CONCLUSIONS: NR stimulates in vitro human BAT but not in vivo BAT in humans. Our research demonstrates the need for further translational research to better understand the differences in NAD+ metabolism in mouse and human.

Brown Adipose Tissue: A Metabolic Regulator in a Hypothalamic Cross Talk?

Since the discovery of functionally competent, energy-consuming brown adipose tissue (BAT) in adult humans, much effort has been devoted to exploring this tissue as a means for increasing energy expenditure to counteract obesity. However, despite promising effects on metabolic rate and insulin sensitivity, no convincing evidence for weight-loss effects of cold-activated human BAT exists to date. Indeed, increasing energy expenditure would naturally induce compensatory feedback mechanisms to defend body weight. Interestingly, BAT is regulated by multiple interactions with the hypothalamus from regions overlapping with centers for feeding behavior and metabolic control. Therefore, in the further exploration of BAT as a potential source of novel drug targets, we discuss the hypothalamic orchestration of BAT activity and the relatively unexplored BAT feedback mechanisms on neuronal regulation. With a holistic view on hypothalamic-BAT interactions, we aim to raise ideas and provide a new perspective on this circuit and highlight its clinical relevance.

Recent developments in natural products for white adipose tissue browning.

Excess accumulation of white adipose tissue (WAT) causes obesity which is an imbalance between energy intake and energy expenditure. Obesity is a serious concern because it has been the leading causes of death worldwide, including diabetes, stroke, heart disease and cancer. Therefore, uncovering the mechanism of obesity and discovering anti-obesity drugs are crucial to prevent obesity and its complications. Browning, inducing white adipose tissue to brown or beige (brite) fat which is brown-like fat emerging in WAT, becomes an appealing therapeutic strategy for obesity and metabolic disorders. Due to lack of efficacy or intolerable side-effects, the clinical trials that promote brown adipose tissue (BAT) thermogenesis and browning of WAT have not been successful in humans. Obviously, more specific means still need to be developed to activate browning of white adipose tissue. In this review, we summarized seven kinds of natural products (alkaloids, flavonoids, terpenoids, long chain fatty acids, phenolic acids, else and extract) promoting white adipose tissue browning which can ameliorate the metabolic disorders, including obesity, dislipidemia, insulin resistance and diabetes. Since natural products are important drug sources and the browning property plays a significant role in not only obesity treatment but also in type 2 diabetes (T2DM) improvement, natural products of inducing browning may be an irreplaceable drug discovery orientation for obesity, diabetes and even other metabolic disorders.

Omega-3 Fatty Acids and Adipose Tissue: Inflammation and Browning.

White adipose tissue (WAT) and brown adipose tissue (BAT) are involved in whole-body energy homeostasis and metabolic regulation. Changes to mass and function of these tissues impact glucose homeostasis and whole-body energy balance during development of obesity, weight loss, and subsequent weight regain. Omega-3 polyunsaturated fatty acids (ω-3 PUFAs), which have known hypotriglyceridemic and cardioprotective effects, can also impact WAT and BAT function. In rodent models, these fatty acids alleviate obesity-associated WAT inflammation, improve energy metabolism, and increase thermogenic markers in BAT. Emerging evidence suggests that ω-3 PUFAs can also modulate gut microbiota impacting WAT function and adiposity. This review discusses molecular mechanisms, implications of these findings, translation to humans, and future work, especially with reference to the potential of these fatty acids in weight loss maintenance.

Feeding brown fat: dietary phytochemicals targeting non-shivering thermogenesis to control body weight.

Excessive adipose accumulation, which is the main driver for the development of secondary metabolic complications, has reached epidemic proportions and combined pharmaceutical, educational and nutritional approaches are required to reverse the current rise in global obesity prevalence rates. Brown adipose tissue (BAT) is a unique organ able to dissipate energy and thus a promising target to enhance BMR to counteract a positive energy balance. In addition, active BAT might support body weight maintenance after weight loss to prevent/reduce relapse. Natural products deliver valuable bioactive compounds that have historically helped to alleviate disease symptoms. Interest in recent years has focused on identifying nutritional constituents that are able to induce BAT activity and thereby enhance energy expenditure. This review provides a summary of selected dietary phytochemicals, including isoflavones, catechins, stilbenes, the flavonoids quercetin, luteolin and resveratrol as well as the alkaloids berberine and capsaicin. Most of the discussed phytochemicals act through distinct molecular pathways e.g. sympathetic nerve activation, AMP-kinase signalling, SIRT1 activity or stimulation of oestrogen receptors. Thus, it might be possible to utilise this multitude of pathways to co-activate BAT using a fine-tuned combination of foods or combined nutritional supplements.

Maternal arginine supplementation enhances thermogenesis in the newborn lamb.

Body temperature maintenance is one of the most important physiological processes initiated after birth. Brown adipose tissue (BAT) is an essential mediator of thermogenesis in many species and is responsible for 50% of the heat generated in the newborn lamb. To determine if maternal arginine supplementation could enhance thermogenesis in the neonate, we randomly assigned 31 multiparous Suffolk ewes, gestating singletons or twins, to receive intravenous injections of either l-arginine (27 mg/kg body weight; n = 17) or sterile saline (n = 14) three times daily from day 75 to 125 of gestation (term = 147). Following parturition, lambs were removed from their mothers and subjected to 0 °C cold challenges at 4 and 22 h of age. Rectal temperatures were higher for the duration of the cold challenges in lambs from arginine-treated ewes compared with lambs from saline-treated ewes (P < 0.05). Elevated rectal temperatures were associated with increased (P < 0.05) circulating glycine and serine concentrations in lambs. The mRNA expression of genes related to BAT function changed over time, but not between lambs from arginine-treated vs. saline-treated ewes. Results indicate that maternal arginine treatment increases neonatal thermogenesis after birth. Although the underlying mechanisms remain to be elucidated, these data are a first step in improving neonatal survival in response to cold.

Grape Extract Activates Brown Adipose Tissue Through Pathway Involving the Regulation of Gut Microbiota and Bile Acid.

SCOPE: Although the physiological function of grape extract (GE) has long been recognized, the precise mechanism remains obscure. This study is designed to investigate the effects of GE on metabolism and the association between GE activation of brown adipose tissue (BAT) and the restoration of gut microbiota (GM). METHODS AND RESULTS: Diet-induced obese mice are used to investigate the function of GE. GE administration increases energy metabolism and prevents obesity. Also, GE restores the dysbiosis of GM by augmenting the observed species, enhancing the Firmicutes-to-Bacteroidetes ratio and increasing the abundance of the Bifidobacteria, Akkermansia, and Clostridia genera. This restoration of GM alters the bile acid (BA) pool in the serum. The abundance of Akkermansia, Clostridium, and Bifidobacterium is negatively correlated with the concentrations of TαMCA, TßMCA, and TCA but is positively correlated with DCA. The changes in BA promoted TGR5 in BAT, which contributed to thermogenesis. The metabolites of GE in blood do not stimulate TGR5 in vitro. CONCLUSION: GE stimulates the thermogenesis of BAT through a pathway involving the regulation of GM and BA in diet-induced obese mice. This study reveals the mechanism by which dietary polyphenols promote thermogenesis by regulating BA, which is altered by GM.

Supplementation of Fermented Barley Extracts with Lactobacillus Plantarum dy-1 Inhibits Obesity via a UCP1-dependent Mechanism.

OBJECTIVE: We aimed to explore how fermented barley extracts with Lactobacillus plantarum dy-1 (LFBE) affected the browning in adipocytes and obese rats. METHODS: In vitro, 3T3-L1 cells were induced by LFBE, raw barley extraction (RBE) and polyphenol compounds (PC) from LFBE to evaluate the adipocyte differentiation. In vivo, obese SD rats induced by high fat diet (HFD) were randomly divided into three groups treated with oral gavage: (a) normal control diet with distilled water, (b) HFD with distilled water, (c) HFD with 800 mg LFBE/kg body weight (bw). RESULTS: In vitro, LFBE and the PC in the extraction significantly inhibited adipogenesis and potentiated browning of 3T3-L1 preadipocytes, rather than RBE. In vivo, we observed remarkable decreases in the body weight, serum lipid levels, white adipose tissue (WAT) weights and cell sizes of brown adipose tissues (BAT) in the LFBE group after 10 weeks. LFBE group could gain more mass of interscapular BAT (IBAT) and promote the dehydrogenase activity in the mitochondria. And LFBE may potentiate process of the IBAT thermogenesis and epididymis adipose tissue (EAT) browning via activating the uncoupling protein 1 (UCP1)-dependent mechanism to suppress the obesity. CONCLUSION: These results demonstrated that LFBE decreased obesity partly by increasing the BAT mass and the energy expenditure by activating BAT thermogenesis and WAT browning in a UCP1-dependent mechanism.

Mitochondrial lipoylation integrates age-associated decline in brown fat thermogenesis.

Thermogenesis in brown adipose tissue (BAT) declines with age; however, what regulates this process remains poorly understood. Here, we identify mitochondria lipoylation as a previously unappreciated molecular hallmark of aged BAT in mice. Using mitochondrial proteomics, we show that mitochondrial lipoylation is disproportionally reduced in aged BAT through a post-transcriptional decrease in the iron-sulfur (Fe-S) cluster formation pathway. A defect in the Fe-S cluster formation by the fat-specific deletion of Bola3 significantly reduces mitochondrial lipoylation and fuel oxidation in BAT, leading to glucose intolerance and obesity. In turn, enhanced mitochondrial lipoylation by α-lipoic acid supplementation effectively restores BAT function in old mice, thereby preventing age-associated obesity and glucose intolerance. The effect of α-lipoic acids requires mitochondrial lipoylation via the Bola3 pathway and does not depend on the anti-oxidant activity of α-lipoic acid. These results open up the possibility to alleviate the age-associated decline in energy expenditure by enhancing the mitochondrial lipoylation pathway.

Sesaminol diglucoside, a water-soluble lignan from sesame seeds induces brown fat thermogenesis in mice.

Brown adipose tissue (BAT) is the site of non-shivering thermogenesis in mammals, wherein energy is dissipated as heat. We observed that aqueous extract of black sesame seed triggers an increase in the expression of Uncoupling Protein 1 (UCP1) in brown adipocytes from mice. The active component from the extract was purified and identified to be sesaminol diglucoside (SDG). SDG treatment decreased mass of white fat pads and serum glucose levels and increased UCP1 levels in BAT thereby protecting mice against high fat induced weight gain. Further in silico and in vitro studies revealed that these effects are due to the agonist like behaviour of SDG towards beta 3 adrenergic receptors (ß3-AR). Together, our results suggest that SDG induces BAT mediated thermogenesis through ß3-AR and protects mice against diet-induced obesity.