Ginsenoside Rg3, enriched in red ginseng extract, improves lipopolysaccharides-induced suppression of brown and beige adipose thermogenesis with mitochondrial activation.

Brown adipose tissue (BAT) which is a critical regulator of energy homeostasis, and its activity is inhibited by obesity and low-grade chronic inflammation. Ginsenoside Rg3, the primary constituent of Korean red ginseng (steamed Panax ginseng CA Meyer), has shown therapeutic potential in combating inflammatory and metabolic diseases. However, it remains unclear whether Rg3 can protect against the suppression of browning or activation of BAT induced by inflammation. In this study, we conducted a screening of ginsenoside composition in red ginseng extract (RGE) and explored the anti-adipogenic effects of both RGE and Rg3. We observed that RGE (exist 0.25 mg/mL of Rg3) exhibited significant lipid-lowering effects in adipocytes during adipogenesis. Moreover, treatment with Rg3 (60 µM) led to the inhibition of triglyceride accumulation, subsequently promoting enhanced fatty acid oxidation, as evidenced by the conversion of radiolabeled 3H-fatty acids into 3H-H2O with mitochondrial activation. Rg3 alleviated the attenuation of browning in lipopolysaccharide (LPS)-treated beige adipocytes and primary brown adipocytes by recovered by uncoupling protein 1 (UCP1) and the oxygen consumption rate compared to the LPS-treated group. These protective effects of Rg3 on inflammation-induced inhibition of beige and BAT-derived thermogenesis were confirmed in vivo by treating with CL316,243 (a beta-adrenergic receptor agonist) and LPS to induce browning and inflammation, respectively. Consistent with the in vitro data, treatment with Rg3 (2.5 mg/kg, 8 weeks) effectively reversed the LPS-induced inhibition of brown adipocyte features in C57BL/6 mice. Our findings confirm that Rg3-rich foods are potential browning agents that counteract chronic inflammation and metabolic complications.

Genistein improves systemic metabolism and enhances cold resistance by promoting adipose tissue beiging.

Genistein, a naturally occurring phytoestrogen and a member of the large class of compounds known as isoflavones, exerts protective effects in several diseases. Recent studies indicate that genistein plays a critical role in controlling body weight, obesity-associated insulin resistance, and metabolic disorders, but its target organs in reversing obesity and related pathological conditions remain unclear. In this study, we showed that mice supplemented with 0.2% genistein in a high-fat diet for 12 weeks showed enhanced metabolic homeostasis, including reduced obesity, improved glucose uptake and insulin sensitivity, and alleviated hepatic steatosis. We also observed a beiging phenomenon in the white adipose tissue and reversal of brown adipose tissue whitening in these mice. These changes led to enhanced resistance to cold stress. Altogether, our data suggest that the improved metabolic profile in mice treated with genistein is likely a result of enhanced adipose tissue function.

Black Raspberry (Rubus coreanus Miquel) Promotes Browning of Preadipocytes and Inguinal White Adipose Tissue in Cold-Induced Mice.

The alteration of white adipose tissue (WAT) "browning", a change of white into beige fat, has been considered as a new therapeutic strategy to treat obesity. In this study, we investigated the browning effect of black raspberry (Rubus coreanus Miquel) using in vitro and in vivo models. Black raspberry water extract (BRWE) treatment inhibited lipid accumulation in human mesenchymal stem cells (hMSCs) and zebrafish. To evaluate the thermogenic activity, BRWE was orally administered for 2 weeks, and then, the mice were placed in a 4 °C environment. As a result, BRWE treatment increased rectal temperature and inguinal WAT (iWAT) thermogenesis by inducing the expression of beige fat specific markers such as PR domain zinc-finger protein 16 (PRDM16), uncoupling protein 1 (UCP1), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), and t-box protein 1 (TBX1) in cold-exposed mice. Furthermore, ellagic acid (EA), a constituent of BRWE, markedly promoted beige specific markers: UCP1, PGC1α, TBX1, and nuclear respiratory factor 1 in beige differentiation media (DM)-induced 3T3-L1 adipocytes. Our findings indicate that BRWE can promote beige differentiation/activation, and EA is the active compound responsible for such effect. Thus, we suggest the nature-derived agents BRWE and EA as potential agents for obesity treatment.

Germinated soy germ extract ameliorates obesity through beige fat activation.

Obesity is a worldwide public health concern requiring safe and effective strategies. Recent studies suggest that bioactive compounds from soybeans have beneficial effects on weight loss and reducing fat accumulation. However, despite the biochemical and nutritional changes during germination, the biological effects of germinated soy germ have not been fully investigated. In this article, germinated soy germ extract (GSGE) was evaluated as a potential treatment option for obesity using 3T3-L1 pre-adipocyte and high-fat diet (HFD)-induced obese mice. In vitro studies demonstrated that GSGE suppressed the differentiation of 3T3-L1 cells into mature adipocytes, along with reductions in lipid accumulation and lipid droplet formation. In vivo studies also showed that a daily dose of 1 mg kg-1 of GSGE reduced weight gain, adipocyte area, serum triglyceride, and LDL-cholesterol in HFD-fed mice. The GSGE treatment promoted browning, which was associated with increased UCP1 expression in vitro and in vivo. In addition, GSGE treatment induced beige fat activation by upregulation of lipolysis and beta-oxidation. Furthermore, gene and protein expression levels of endocannabinoid system-related factors such as NAPE-PLD, FAAH, DAGL-α, and CB2 were altered along with browning and beige fat activation by GSGE. The present study indicates that GSGE effectively inhibits lipid accumulation and promotes beige fat transition and activation. Therefore, we suggest that GSGE treatment could be a promising strategy for the prevention of obesity by promoting weight loss, reducing fat accumulation, and improving obesity-related metabolic disorders.

Fish oil as a potential activator of brown and beige fat thermogenesis.

Numerous studies have shown that feeding rodents n-3 polyunsaturated fatty acids attenuates adiposity. Moreover, meta-analyses of human dietary intervention studies indicate that fish oil (eicosapentaenoic and docosahexaenoic acid) supplementation might reduce waist circumference. A recent line of research suggests that browning of white adipose depots and activation of uncoupled respiration in brown fat contributes to these effects. This mini-review summarizes the observations in rodents, highlights several mechanisms that might explain these observations and discusses the translational potential. Given the available in vivo evidence and the ability of human adipocytes to aquire a beige phenotype in response to eicosapentaenoic acid incubation, future studies should test the hypothesis that fish oil activates thermogenic brown and beige adipose tissue in humans.

Dietary Factors Promoting Brown and Beige Fat Development and Thermogenesis.

Brown adipose tissue (BAT) is a specialized fat tissue that has a high capacity to dissociate cellular respiration from ATP utilization, resulting in the release of stored energy as heat. Adult humans possess a substantial amount of BAT in the form of constitutively active brown fat or inducible beige fat. BAT activity in humans is inversely correlated with adiposity, blood glucose concentrations, and insulin sensitivity; this suggests that strategies aimed at BAT-mediated bioenergetics are an attractive therapeutic target in combating the continuing epidemic of obesity and diabetes. Despite advances in knowledge regarding the developmental lineage and transcriptional regulators of brown and beige adipocytes, our current understanding of environmental modifiers of BAT thermogenesis, such as diet, is limited. In this review, we consolidated the latest research on dietary molecules that may serve to promote BAT thermogenesis. Here, we summarized the thermogenic function of selected phytochemicals (e.g., capsaicin, resveratrol, curcumin, green tea, and berberine), dietary fatty acids (e.g., fish oil and conjugated linoleic acids), and all-trans retinoic acid, a vitamin A metabolite. We also delineated the proposed mechanisms whereby these dietary molecules promote BAT activity and/or browning of white adipose tissue. Characterizing thermogenic dietary factors may offer novel insight into revising nutritional intervention strategies aimed at obesity and diabetes prevention and management.