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.
Highlights
Obesity is caused by an imbalance between energy intake and energy expenditure
We investigated whether WS 70% ethanol extract (WSE) supplementation would exhibit an anti-obesity effect in high-fat diet (HFD)-fed mice
WSE supplementation significantly suppressed the increase in serum triglyceride induced by HFD, and the serum high-density lipoprotein/total cholesterol ratio was significantly increased by this supplementation (Figure 1B)
Summary
Obesity is caused by an imbalance between energy intake and energy expenditure. When the energy expenditure exceeds the intake, this leads to weight loss [1]. Energy expenditure comprises the basal metabolic rate, physical activity (exercise-induced), and adaptive thermogenesis (shivering, non-shivering, and diet-induced) [2]. Recent studies have suggested that adaptive thermogenesis is a new therapeutic approach to treating obesity [3]. Adaptive thermogenesis occurs mainly in brown adipose tissue (BAT) and skeletal muscle [4]. The various phytochemicals in medicinal plants have been reported to ameliorate obesity through promoting mitochondrial biogenesis and thermogenesis in adipose tissue [5,6]
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