Cyclocarya paliurus (Batal.) Ijinskaja Aqueous Extract (CPAE) Ameliorates Obesity by Improving Insulin Signaling in the Hypothalamus of a Metabolic Syndrome Rat Model

BACKGROUND: Antiobesity drugs may not be optimal for treating obesity. However novel antiobesity agents, especially those derived from natural products, may be suitable. Therefore, we investigated the effects and mechanisms of Cyclocarya paliurus (CP) aqueous extract (CPAE) on obesity. METHODS: SHR.Cg-Leprcp/NDmcr (SHR/cp) rats were used as a model of obesity and metabolic syndrome. Experimental animals were allocated into two groups—control and CPAE (0.5 g/kg)—for a 7-week treatment period. Examinations were performed, including general physiological characteristics, obesity-related biochemical parameters, and insulin-signaling pathway-related proteins in the hypothalamus. RESULTS: Treatment with CPAE reduced food intake, body weight, organ weight, fat mass, and body mass index (BMI) in SHR/cp rats. Meanwhile, CPAE also decreased the levels of fasting serum glucose, fasting serum insulin, HOMA-IR, serum free fatty acids, serum malondialdehyde, serum superoxide dismutase, and serum total-glutathione. The levels of phosphorylation of target proteins—including InsR, IRS1, PI3Kp85, Akt, and FoXO1 as well as protein expression of POMC—were significantly upregulated in the hypothalamus, but NPY expression remarkably decreased. CONCLUSIONS: CPAE has antiobesity, antihypoglycemic, antihypolipidemic, and antioxidant properties. The mechanism responsible for the antiobesity effect of CPAE may be related to suppression of energy intake via regulation of insulin-signaling pathway in the hypothalamus.