## 3 Effect of PS on Components of MetS
### Effect of PS on Obesity
The actions of PS on adiponectin and leptin suggest it can influence satiety and adipose accumulation in the body. PS aqueous leaves extract (1.25 mg/kg/day for 5 months) reduced the activity of 11\(\beta\)HSD-1 in the liver and adipose tissue of ovariectomy-induced obese female rats [53]. This observation suggests that PS supplementation prevents obesity by inhibiting 11\(\beta\)HSD-1 expression and activity, subsequently reducing adipocyte hypertrophy. The aqueous and methanolic leaf extracts of PS increased the circulating adiponectin levels in rats with ovariectomy-induced obesity [67] and fructose-induced MetS rats [68], suggesting that PS could prevent MetS and its components through up-regulating adiponectin levels. The metabolic leaf extract of PS reduced leptin levels in fructose-induced MetS rats [68]. Concurrently, food, fluid, and calorie intakes were reduced in MetS rats treated with methanolic extract of PS leaf, leading to a reduction in body adiposity and body weight [68]. These observations implied that PS supplementation reduced leptin resistance in MetS rats, which subsequently inhibited hunger, leading to a decreased fat mass and body weight. Meanwhile, the aqueous leaf extract of PS did not change the body weight in ovariectomy-induced obese rats [53; 67]. Leptin resistance is also associated with increased oxidative stress [69]. Cell culture and animal studies demonstrated that oxidative stress increases adipocyte differentiation, hyperplasia, and hypertrophy, potentially leading to obesity [70; 71; 72]. [PERSON] et al. [68] suggested that the decrease in adipocyte size in fructose-induced MetS rats could be due to the antioxidant effects of active compounds in PS. However, this speculation has yet to be tested by any studies. Overall, the current evidence suggests that PS supplementation inhibits obesity by regulating adipokine and leptin levels. Notably, leptin resistance was prevented by PS supplementation, leading to the suppression of food and calorie intake [68]. The reduction in calorie intake prevents adipocyte hypertrophy, increased body weight, and adiposity [68]. On the other hand, PS could suppress 11\(\beta\)HSD-1 activity and oxidative stress, leading to reduced adiposity [68]. To bridge the research gaps of this topic, the authors suggest combining calorie restriction and PS supplementation in future studies to assess the combinatorial interventions on obesity. This is because calorie restriction was shown to be the most effective dietary intervention for weight loss in humans [73]. Since the methanolic PS leaf extract effectively decreased body weight and calorie intake in fructose-induced MetS rats via regulating leptin and adiponectin levels [68], the combination could speed up weight loss in obese subjects. Furthermore, oxidative stress has been linked with increased adipocyte differentiation (adipogenesis). Further studies should examine adipogenesis markers, such as CCAAT/enhancer binding protein (CEBP)-\(\alpha\), -\(\beta\), and peroxisome proliferatorator activator receptor (PPAR)-\(\gamma\), to establish the effect of PS supplementation on adipocytes formation. Figure 2 summarises the current knowledge on the effect of PS supplementation on obesity and the further investigation required in this area.