Rutin ameliorates obesity through brown fat activation

Abstract

Increasing energy expenditure through activation of brown adipose tissue (BAT) is a critical approach to treating obesity and diabetes. In this study, rutin, a natural compound extracted from mulberry and a drug used as a capillary stabilizer clinically for many years without any side effects, regulated whole-body energy metabolism by enhancing BAT activity. Rutin treatment significantly reduced adiposity, increased energy expenditure, and improved glucose homeostasis in both genetically obese (Db/Db) and diet-induced obesity (DIO) mice. Rutin also induced brown-like adipocyte (beige) formation in subcutaneous adipose tissue in both obesity mouse models. Mechanistically, we found that rutin directly bound to and stabilized SIRT1, leading to hypoacetylation of peroxisome proliferator-activated receptor γ coactivator-1α protein, which stimulated Tfam transactivation and eventually augmented the number of mitochondria and UCP1 activity in BAT. These findings reveal that rutin is a novel small molecule that activates BAT and may provide a novel therapeutic approach to the treatment of metabolic disorders.-Yuan, X., Wei, G., You, Y., Huang, Y., Lee, H. J., Dong, M., Lin, J., Hu, T., Zhang, H., Zhang, C., Zhou, H., Ye, R., Qi, X., Zhai, B., Huang, W., Liu, S., Xie, W., Liu, Q., Liu, X., Cui, C., Li, D., Zhan, J., Cheng, J., Yuan, Z., Jin, W. Rutin ameliorates obesity through brown fat activation.

Guarana supplementation attenuated obesity, insulin resistance, and adipokines dysregulation induced by a standardized human Western diet via brown adipose tissue activation

“…In the present study, guarana activated BAT by promoting mass increase, mitochondrial biogenesis, and UCP1 overexpression, which are important mechanisms of BAT activation (Lidell et al, ; Sanchez‐Delgado et al, ). Corroborating our data, many other extracts/compounds effective in weight management have been shown to activate BAT in humans and animal models (Saito & Yoneshiro, ; Yoneshiro et al, ; Yuan et al, ). BAT activation can be stimulated by other factor like ambient temperature, which is a crucial factor in determining organismal energy balance, at least in part through BAT activation (Lidell et al, ; Sanchez‐Delgado et al, ).…”

“…Currently, many key factors have been widely used to indicate BAT activation, such as BAT expansion, UCP1 content, and mitochondrial numbers (Lidell, Betz, & Enerbäck, 2014;Sanchez-Delgado et al, 2015). It is known that many plants (extracts and phytochemicals) are able to activate the BAT (Saito & Yoneshiro, 2013;Yoneshiro et al, 2017;Yuan et al, 2017). Thus, these plants become an attractive therapeutic targets to treat obesity.…”

Cyanidin‐3‐glucoside increases whole body energy metabolism by upregulating brown adipose tissue mitochondrial function

“…Activation of PGC1‐α plays an important role in mitochondrial biogenesis and SIRT1‐mediated PGC1‐α deacetylation and activation is critical for mitochondrial function in BAT . Several polyphenols from plant extract, such as resveratol and rutin are known to directly stimulate BAT thermogenesis and promote WAT browning by increasing expression and activation of SIRT1 . In this study, we found that C3G treatment could markedly increase mtDNA copy number, PGC1‐α, TFAM , and NRF1/2 expression both in BAT and sWAT (Figs.…”

“…However, while supplements at this dose (1320 mg) and higher are readily available in pill or capsule form for general public consumption, we do not advocate their usage. In addition to C3G, there were a number of other bioactive substances (such as resveratrol and rutin) in our daily diet . Therefore, other bioactive compounds in our daily diet may work in concert with single purified C3G to improve the BAT activity.…”

“…The Inveon Acquisition Workplace (IAW) software was used for scanning process. The PET‐CT instrument parameters and the data analysis referred to our previous method .…”