Withania somnifera Extract Enhances Energy Expenditure via Improving Mitochondrial Function in Adipose Tissue and Skeletal Muscle

Abstract

Withania somnifera (WS), commonly known as ashwagandha, possesses diverse biological functions. WS root has mainly been used as an herbal medicine to treat anxiety and was recently reported to have an anti-obesity effect, however, the mechanisms underlying its action remain to be explored. We hypothesized that WS exerts its anti-obesity effect by enhancing energy expenditure through improving the mitochondrial function of brown/beige adipocytes and skeletal muscle. Male C57BL/6J mice were fed a high-fat diet (HFD) containing 0.25% or 0.5% WS 70% ethanol extract (WSE) for 10 weeks. WSE (0.5%) supplementation significantly suppressed the increases in body weight and serum lipids, and lipid accumulation in the liver and adipose tissue induced by HFD. WSE supplementation increased oxygen consumption and enhanced mitochondrial activity in brown fat and skeletal muscle in the HFD-fed mice. In addition, it promoted browning of subcutaneous fat by increasing mitochondrial uncoupling protein 1 (UCP1) expression. Withaferin A (WFA), a major compound of WS, enhanced the differentiation of pre-adipocytes into beige adipocytes and oxygen consumption in C2C12 murine myoblasts. These results suggest that WSE ameliorates diet-induced obesity by enhancing energy expenditure via promoting mitochondrial function in adipose tissue and skeletal muscle, and WFA is a key regulator in this function.

Differential effects of pre‐exercise on cancer cachexia‐induced muscle atrophy in fast‐ and slow‐twitch muscles

“…CS activity and mitochondrial respiratory capacity are indicators of mitochondrial function, and SIRT1 is a key regulator of mitochondrial function. 44,54,55 One previous study found that CS activity in slow-twitch muscle is higher than that in the fast-twitch muscle, 56 which is consistent with our findings. In addition, mitochondrial dysfunction through decreased SIRT1 expression is caused by increased levels of inflammatory cytokines generating higher levels of ROS.…”

“…54,55,57 Furthermore, ROS are produced as a by-product of mitochondrial respiration. 58 Reduced mitochondrial respiratory capacity leads to increased ROS production 44,59 and vice versa, eventually leading to a further increase in ROS production. 60 Moreover, the mitochondrion has a ROS scavenging ability that depends on mitochondrial function.…”

<p>The Mechanism of Traditional Chinese Medicine for the Treatment of Obesity</p>

“…36 Withania somnifera extract (WSE) increases oxygen consumption and enhances the expression of BAT genes, including UCP1, PGC1α, type II iodothyronine deiodinase (DiO2) and cytochrome c oxidase 8b subunit (Cox8b), and promotes the browning of subcutaneous adipose tissue in mice fed a high-fat diet. 37…”

Lesser Investigated Natural Ingredients for the Management of Obesity

“…These results were observed along with attenuation of hepatic inflammation, oxidative stress, and insulin resistance in mice [ 147 ]. An ethanol extract of WS enriched with Withaferin A was found to suppress increases in bodyweight, serum lipids, and lipid accumulation in the liver and promote browning of subcutaneous fat in mice by increasing mitochondrial uncoupling protein 1 (UCP1) expression [ 148 ]. Withania somnifera extract was also found to increase energy expenditure by increasing oxygen consumption and thermogenesis in HFD-fed mice.…”