ATP-Binding Cassette Protein ABCC10 Deficiency Prevents Diet-Induced Obesity but Not Atherosclerosis in Mice

Abstract

Excess plasma lipid levels are a risk factor for various cardiometabolic disorders. Studies have shown that improving dyslipidemia lowers the progression of these disorders. In this study, we investigated the role of ATP-binding cassette transporter C10 (ABCC10) in regulating lipid metabolism. Our data indicate that deletion of the Abcc10 gene in male mice results in lower plasma and intestinal triglycerides by around 38% and 36%, respectively. Furthermore, deletion of ABCC10 ameliorates diet-induced obesity in mice and leads to a better response during insulin and glucose tolerance tests. Unexpectedly, ABCC10 deficiency does not affect triglyceride levels or atherosclerosis in ApoE-deficient mice. In addition, our studies demonstrate low oleate uptake by enterocytes (~25–30%) and less absorption (~37%) of triglycerides in the small intestine of ABCC10 knockout mice. Deletion of the Abcc10 gene also alters several lipid metabolism genes in the intestine, suggesting that ABCC10 regulates dietary fat absorption, which may contribute to diet-induced obesity in mice.

Keywords

• diet-induced obesity
• type 2 diabetes
• atherosclerosis
• lipid metabolism
• triglyceride absorption