Kaempferide improves glycolipid metabolism disorder by activating PPARγ in high-fat-diet-fed mice

Abstract

AimsKaempferide (Ka, 3,5,7-trihydroxy-4′-methoxyflavone), an active ingredient of Tagetes erecta L., has been demonstrated to possess many pharmacological effects, including antioxidant, anti-inflammation, anticancer and antihypertension in previous study. However, there is no evidence of Ka on metabolic disorder in former studies. This study investigated the effects of Ka on glycolipid metabolism and explored the underlying mechanisms of action in vivo and vitro. Materials and methodsThe mouse model of glycolipid metabolism disorder was induced by high-fat diet (HFD). The effects of Ka were evaluated on bodyweight, lipid metabolism and glucose metabolism. Hypolipidemic effect was examined by blood sample analysis. The hypoglycemic effect was detected by several indicators, like blood glucose, serum insulin, HOMA index and intraperitoneal glucose tolerance tests (IPGTT). The signaling pathways of lipid metabolism (PPARγ/LXRα/ABCA1) and glucose metabolism (PPARγ/PI3K/AKT) were evaluated using Real-Time PCR and Western blot. The primary culture of hepatocyte was prepared to confirm the target of Ka by co-culturing with PPARγ agonist or inhibitor. Key findingsThe HFD mice developed obesity, hyperlipidemia, hyperglycemia and insulin resistance. Administration of Ka at a dose of 10 mg/kg.BW for 16 weeks effectively attenuated these changes. Further studies revealed the hypolipidemic and hypoglycemic effects of Ka depended on the activation of PPARγ/LXRα/ABCA1 and PPARγ/PI3K/AKT pathways, respectively. The primary hepatocyte test, co-cultured with PPARγ agonists or inhibitors, further confirmed the above signaling pathway and key protein. SignificanceThese results suggested that Ka played an important role in improving glycolipid metabolism disorder. These favorable effects were causally associated with anti-obesity. The underlying mechanisms might have to do with the activation of the PPARγ and its downstream signaling pathway. Our study helped to understand the pharmacological actions of Ka, and played a role for Ka in the effective treatment of obesity, diabetes, nonalcoholic hepatitis and other metabolic diseases.