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Obesity is a chronic disease derived from disequilibrium between energy intake and energy expenditure and evolving as a challenging epidemiological disease in the 21st century. It is urgently necessary to solve this issue by searching for effective strategies and safe drugs. Skeletal muscle could be a potential therapeutic target for the prevention and treatment of obesity and its associated complications due to non-shivering thermogenesis (NST) function. Skeletal muscle NST is based dominantly on futile sarcoplasmic reticulum Ca 2+ ATPase (SERCA) pump cycling that leads to a rise in cytosolic Ca 2+ , increased adenosine triphosphate (ATP) hydrolysis and heat production. This review will highlight the mechanisms of skeletal muscle NST, including SLN mediated SERCA pump futile cycling, SR-mitochondrial crosstalk and increased mitochondrial biogenesis, and thermogenesis induced by uncoupling proteins 3 (UCP3). We then summarize natural products targeting the pathogenesis of obesity via skeletal muscle NST, offering new insights into pharmacotherapy and potential drug candidates to combat obesity., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Obesity is a chronic metabolic disease caused by a long-term imbalance between energy intake and expenditure. The discovery of three different shades of adipose tissues has implications in terms of understanding the pathogenesis and potential interventions for obesity and its related complications. Fat browning, as well as activation of brown adipocytes and new beige adipocytes differentiated from adipogenic progenitor cells, are emerging as interesting and promising methods to curb obesity because of their unique capacity to upregulate non-shivering thermogenesis. This capacity is due to catabolism of stored energy to generate heat through the best characterized thermogenic effector uncoupling protein 1 (UCP1). A variety of phytochemicals have been shown in the literature to contribute to thermogenesis by acting as chemical uncouplers, UCP1 inducers or regulators of fat differentiation and browning. In this review, we summarize the mechanisms and strategies for targeting adipose-mediated thermogenesis and highlight the role of phytochemicals in targeting adipose thermogenesis to fight against obesity. We also discuss proposed targets for how these phytochemical molecules promote BAT activity, WAT browning and beige cell development, thereby offering novel insights into interventional strategies of how phytochemicals may help prevent and manage obesity via adipose thermogenesis., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: The mechanism by which Roux-en-Y Gastric Bypass (RYGB) increases the secretion of glucagon-like peptide-1 (GLP-1) remains incompletely defined. Here we investigated whether TGR5-mTORC1 signaling mediates the RYGB-induced alteration in GLP-1 production in mice and human beings., Methods: Circulating bile acids, TGR5-mTORC1 signaling, GLP-1 synthesis and secretion were determined in lean or obese male C57BL/6 mice with or without RYGB operation, as well as in normal glycemic subjects, obese patients with type 2 diabetes before and after RYGB., Results: Positive relationships were observed among circulating bile acids, ileal mechanistic target of rapamycin complex 1 (mTORC1) signaling and GLP-1 during changes in energy status in the present study. RYGB increased circulating bile acids, ileal Takeda G protein-coupled receptor 5 (TGR5) and mTORC1 signaling activity, as well as GLP-1 production in both mice and human subjects. Inhibition of ileal mTORC1 signaling by rapamycin significantly attenuated the stimulation of bile acid secretion, TGR5 expression and GLP-1 synthesis induced by RYGB in lean and diet-induced obese mice. GLP-1 production and ileal TGR5-mTORC1 signaling were positively correlated with plasma deoxycholic acid (DCA) in mice. Treatment of STC-1 cells with DCA stimulated the production of GLP-1. This effect was associated with a significant enhancement of TGR5-mTORC1 signaling. siRNA knockdown of mTORC1 or TGR5 abolished the enhancement of GLP-1 synthesis induced by DCA. DCA increased interaction between mTOR-regulatory-associated protein of mechanistic target of rapamycin (Raptor) and TGR5 in STC-1 cells., Interpretation: Deoxycholic acid-TGR5-mTORC1 signaling contributes to the up-regulation of GLP-1 production after RYGB., (Copyright © 2018. Published by Elsevier B.V.)

Epitranscriptome (RNA modification) plays a vital role in a variety of biological events. N6-methyladenosine (m6A) modification is the most prevalent mRNA modification in eukaryotic cells. Dynamic and reversible m6A modification affects the plasticity of epitranscriptome, which plays an essential role in lipid metabolism. In this review, we comprehensively delineated the role and mechanism of m6A modification in the regulation of lipid metabolism in adipose tissue and liver, and summarized phytochemicals that improve lipid metabolism disturbance by targeting m6A regulator, providing potential lead candidates for drug therapeutics. Moreover, we discussed the main challenges and possible future directions in this field. [ABSTRACT FROM AUTHOR]