Perfluorodecanoic acid promotes high-fat diet-triggered adiposity and hepatic lipid accumulation by modulating the NLRP3/caspase-1 pathway in male C57BL/6J mice

Abstract

Perfluorodecanoic acid (PFDA), a chemical contaminant, may casue became obesity, which makes it a public health concern. In this study, we investigated the effects of PFDA on adiposity development and hepatic lipid accumulation in mice fed with a high-fat diet (HFD). Animals were assigned to two diet treatments (low-fat and high-fat); and PFDA was administered through drinking water for 12 weeks. The contaminant promoted body weight gain and adiposity in HFD-fed mice. Moreover, HFD-fed mice exposed to PFDA had impaired glucose metabolism, inflammation and hepatic lipid accumulation compared to mice fed HFD alone. PFDA activated the expression of hepatic NLRP3 and caspase-1, and induced that of SREBP-1c expression in the liver of HFD-fed mice. PFDA exposure in HFD-fed mice significantly inhibited hepatic AMPK expression than animals fed HFD without PFDA exposure. Furthermore, MCC950, an NLRP3 inhibitor, suppressed the upregulation of NLRP3 and caspase-1 expression, and inhibited the expression of SREBP-1c and the accumulation of hepatic lipid in mice exposed to PFDA. Thus, PFDA may enhance HFD-induced adiposity and hepatic lipid accumulation through the NLRP3/caspase-1 pathway. This contaminant may be a key risk factor for obesity development in individuals consuming high-fat foods, particularly Western diet.

Keywords: Adiposity; Food chemical contaminant; Insulin resistance; NLRP3 inflammasome; Perflfluorodecanoic acid.