Increasing evidence indicates that brown adipose tissue (BAT) transplantation enhances whole-body energy metabolism in a mouse model of diet-induced obesity. However, it remains unclear whether BAT also has such beneficial effects on genetically obese mice. To address this issue, we transplanted BAT from C57/BL6 mice into the dorsal subcutaneous region of age- and sex-matched leptin deficient Ob/Ob mice. Interestingly, BAT transplantation led to a significant reduction of body weight gain with increased oxygen consumption and decreased total body fat mass, resulting in improvement of insulin resistance and liver steatosis. In addition, BAT transplantation increased the level of circulating adiponectin, whereas it reduced the levels of circulating free T3 and T4, which regulate thyroid hormone sensitivity in peripheral tissues. BAT transplantation also increased β3-adrenergic receptor and fatty acid oxidation related gene expression in subcutaneous and epididymal (EP) white adipose tissue. Accordingly, BAT transplantation increased whole-body thermogenesis. Taken together our results demonstrate that BAT transplantation may reduce obesity and its related diseases by activating endogenous BAT.

Myricetin (3,5,7-trihydroxy-2-(3,4,5-tri hydroxyphenyl)-4-benzopyrone) is a common flavonol extracted from many natural plants and Chinese herb medicines and has been demonstrated to have multiple pharmacological activities, such as anti-microbial, anti-thrombotic, neuroprotective, and anti-inflammatory effects. Previously, myricetin was reported to target Mpro and 3CL-Pro-enzymatic activity to SARS-CoV-2. However, the protective value of myricetin on SARS-Cov-2 infection through viral-entry facilitators has not yet been comprehensively understood.

Interorganelle contacts facilitate material exchanges and sustain the structural and functional integrity of organelles. Lipid droplets (LDs) of adipocytes are responsible for energy storage and mobilization responding to body needs. LD biogenesis defects compromise the lipid-storing capacity of adipocytes, resulting in ectopic lipid deposition and metabolic disorders, yet how the uniquely large LDs in adipocytes attain structural and functional maturation is incompletely understood. Here we show that the mammalian adipocyte-specific protein CLSTN3B is crucial for adipocyte LD maturation. CLSTN3B employs an arginine-rich segment to promote extensive contact and hemifusion-like structure formation between the endoplasmic reticulum (ER) and LD, allowing ER-to-LD phospholipid diffusion during LD expansion. CLSTN3B ablation results in reduced LD surface phospholipid density, increased turnover of LD-surface proteins, and impaired LD functions. Our results establish the central role of CLSTN3B in the adipocyte-specific LD maturation pathway that enhances lipid storage and maintenance of metabolic health under caloric overload.

With rapid economic development, the prevalence of obesity has increased remarkably worldwide. Obesity can induce a variety of metabolic diseases, such as atherosclerosis, diabetes, hypertension and coronary heart disease, which significantly endanger the health and welfare of individuals. Brown and beige fat tissues play an important role in thermogenesis in mammals. Recent studies have shown that follistatin (FST) can potentially induce the browning of white adipose tissue (WAT). In this study, high-fat diet-induced obese mice were injected with follistatin for one week to explore the effects of follistatin on browning and metabolism and to determine the mechanism. The results showed that follistatin suppressed obesity caused by a high-fat diet and increased insulin sensitivity, energy expenditure, and subcutaneous fat browning. The beneficial effects remained even after a period of withdrawal. Follistatin promoted secretion of irisin from subcutaneous fat via the AMPK-PGC1α-irisin signal pathway, which induces browning of WAT, and activated the insulin pathway in beige fat thereby promoting metabolism.

As a thermogenic organ, brown adipose tissue (BAT) has received a great attention in treating obesity and related diseases. It has been reported that brown adipocyte was derived from engrailed-1 (EN1) positive central dermomyotome. However, functions of EN1 in brown adipogenesis are largely unknown. Here we demonstrated that EN1 overexpression increased while EN1 knockdown decreased lipid accumulation and the expressions of key adipogenic genes including PPARγ2 and C/EBPα and mitochondrial OXPHOS as well as BAT specific marker UCP1. Taken together, our findings clearly indicate that EN1 is a positive regulator of brown adipogenesis.

Improvement of hyperglycemia through dietotherapy/herbal remedy is an effective approach to treating diabetes. In this study, mulberry leaf, famous for silkworm's special food and therapeutic value without any side effects, alleviated diabetes by attenuating NEFA signaling and modulating intestinal microflora. Mulberry leaf treatment significantly reduce fasting blood-glucose and HbA1c, ameliorate the blood lipid profile and improve insulin resistance in streptozotocin-induced diabetic rats. Mechanistically, we found that mulberry leaf inhibited NEFA signaling by reducing downstream signaling in the NEFA pathway, further verified by reduced PKC and improved cellular energy homeostasis based on restored expression of PGC-1α, AK2, OXPHOS and adiponectin. Mulberry leaf treatment also restored the phyla Bacteroidetes and Proteobacteria and class Clostridia, which were associated with insulin resistance and diabetes. Our findings reveal that mulberry leaf is an edible with therapeutic potential for diabetes and may provide a novel dietotherapy/herbal remedy to the treatment of diabetes.

Alliin (S-allyl cysteine sulfoxide) is a bioactive sulfoxide compound derived from garlic. To evaluate the preventive effect of alliin against metabolic risk factors in diet induced obese (DIO) mice, we treated the C57BL/6J DIO mice with drinking water with or without alliin (0.1 mg/ml) for 8 weeks. Results showed that alliin had no significant effect on the body weight, adiposity or energy balance. However, alliin treatment enhanced glucose homeostasis, increased insulin sensitivity and improved the lipid profile in the DIO mice. This was, at least partly, attributable to alliin induced modulation of the intestinal microbiota composition, typically decreased Lachnospiraceae and increased Ruminococcaceae. From above, we conclude that alliin has nutraceutical or even medicinal potential in prevention of diabetes and lipid metabolic disorders.

Polycystic ovary syndrome (PCOS) is a common metabolic and endocrine disease affecting women of reproductive age. Due to its complex aetiology, there is no currently effective cure for PCOS. Brown adipose tissue (BAT) activity is significantly decreased in PCOS patients, and BAT activation has beneficial effects in animal models of PCOS. Here, we investigated the effect of ginsenoside compound K (CK) in an animal model of PCOS and its mechanism of BAT activation.

Brown adipose tissue (BAT) plays an essential role in maintaining body temperature and in treating obesity and diabetes. The adult BAT (aBAT) and neonatal BAT (neBAT) vary greatly in capacity, but the characteristics and differences between them on the molecular level, as well as the related features of BAT as it develops post-delivery, have not yet been fully determined. In this study, we examined the morphological features of aBAT and neBAT of mice by using hematoxylin-eosin (H&E) staining, transmission electron microscopy (TEM), and scanning electron microscopy (SEM). We found that neBAT contains a smaller number and size of lipid droplets, as well as more abundant mitochondria, compared with aBAT. The dynamic morphological changes revealed that the number and size of lipid droplets increase, but the number of mitochondria gradually decrease during the post-delivery development, which consisted of some differences in RNA or protein expression levels, such as gradually decreased uncoupling protein 1 (UCP1) expression levels and mitochondrial genes, such as mitochondrial transcription factor A (Tfam). The adipocyte differentiation-related genes, such as transcription factor CCAAT enhancer-binding protein β (CEBPβ), were also continuously upregulated. Additionally, the different features of aBAT and neBAT were analyzed from the global transcription (RNA-Seq) level, which included messenger RNA (mRNA), microRNA, long non-coding RNA (lncRNA), circRNA, and DNA methylation, as well as proteins (proteomics). Differentially methylated region (DMR) analysis identified 383 hyper- and 503 hypo-methylated genes, as well as 1221 new circRNA in ne-BAT and 1991 new circRNA in a-BAT, with significantly higher expression of circRNA in aBAT compared with neBAT. Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that mitochondrial activity, protein synthesis, and cell life activity levels were higher in neBAT, and pathways related to ribosomes, spliceosomes, and metabolism were significantly activated in neBAT compared to aBAT. Collectively, this study describes the dynamic changes occurring throughout post-delivery development from the morphological, molecular and omics perspectives. Our study provides information that may be utilized in improving BAT functional activity through gene regulation and/or epigenetic regulation.

Traditional Chinese medicine (TCM) has been long time used in China and gains ever-increasing worldwide acceptance. Er Miao San (EMS), a TCM formula, has been extensively used to treat inflammatory diseases, while its bioactive components and therapeutic mechanisms remain unclear. In this study, we conducted an integrative approach of network pharmacology and experimental study to elucidate the underlying mechanisms of EMS in treating human rheumatoid arthritis (RA) and other inflammatory conditions. Quercetin, wogonin and rutaecarpine were probably the main active compounds of EMS in RA treatment as they affected the most RA-related targets, and TNF-α, IL-6 and IL-1β were considered to be the core target proteins. The main compounds in EMS bound to these core proteins, which was further confirmed by molecular docking and bio-layer interferometry (BLI) analysis. Moreover, the potential molecular mechanisms of EMS predicted from network pharmacology analysis, were validated in vivo and in vitro experiments. EMS was found to inhibit the production of NO, TNF-α and IL-6 in lipopolysaccharide (LPS)-stimulated RAW264.7 cells; reduce xylene-induced mouse ear edema; and decrease the incidence of carrageenan-induced rat paw edema. The carrageenan-induced up-regulation of TNF-α, IL-6 and IL-1β mRNA expression in rat paws was down-regulated by EMS, consistent with the network pharmacology results. This study provides evidence that EMS plays a critical role in anti-inflammation via suppressing inflammatory cytokines, indicating that EMS is a candidate herbal drug for further investigation in treating inflammatory and arthritic conditions.

Brown adipose tissue (BAT), an organ that burns energy through uncoupling thermogenesis, is a promising therapeutic target for obesity. However, there are still no safe anti-obesity drugs that target BAT in the market. In the current study, we performed large scale screening of 636 compounds which were approved by Food and Drug Administration (FDA) to find drugs that could significantly increase uncoupling protein 1 (UCP1) mRNA expression by real-time PCR. Among those UCP1 activators, most of them were antibiotics or carcinogenic compounds. We paid particular attention to fluvastatin sodium (FS), because as an inhibitor of the cellular hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase, FS has already been approved for treatment of hypercholesteremia. We found that in the cellular levels, FS treatment significantly increased UCP1 expression and BAT activity in human brown adipocytes. Consistently, the expression of oxidative phosphorylation-related genes was significantly increased upon FS treatment without differences in adipogenic gene expression. Furthermore, FS treatment resisted to high-fat diet (HFD)-induced body weight gain by activating BAT in the mice model. In addition, administration of FS significantly increased energy expenditure, improved glucose homeostasis and ameliorated hepatic steatosis. Furthermore, we reveal that FS induced browning in subcutaneous white adipose tissue (sWAT) known to have a beneficial effect on energy metabolism. Taken together, our results clearly demonstrate that as an effective BAT activator, FS may have great potential for treatment of obesity and related metabolic disorders.

Obesity is associated with disrupted energy homeostasis and intestinal dysbiosis. Caulis Spatholobi, traditional Chinese medicine for herbal therapy, contains a wide range of bioactive compounds and has a specific pharmacological function. However, its effects on obesity and related metabolic disorder have remained largely unexplored. In this study, we showed that the water extract of Caulis Spatholobi (WECS) has a significant effect in inhibiting body weight gain, decreasing adiposity, maintaining glucose homeostasis, reducing insulin resistance and improving hepatic steatosis in diet-introduced obesity (DIO) mice. Besides, the administration of WECS significantly increased the expression levels of genes involved in the brown adipose tissue (BAT) activation and thermogenesis in DIO mice. Also, the activation of BAT treated with WECS was also confirmed in BAT primary cells. Mechanisms, the improvement of glucose homeostasis and insulin resistance may be related to the upregulated MAPK and AMPK pathways in white adipose tissue (WAT) and BAT. Notably, WECS also improved the obesity-induced gut microbiota dysbiosis, which induced an increase of anti-obesity and anti-diabetes related bacteria genus. In conclusion, Caulis Spatholobi can ameliorate obesity through activating brown adipose tissue and modulating the composition of gut microbiota. Our findings provide a novel perspective on Chinese medicine applications and provide a promising therapeutic approach for the treatment of obesity and metabolic disorders.