Leptin Contributes to the Adaptive Responses of Mice to High-Fat Diet Intake through Suppressing the Lipogenic Pathway

• DOI: 10.1371/journal.pone.0006884
• Publication Date: 2009-09-02T22:43:47Z
• Authors: Lei Jiang; Qiong Wang; Yue Yu; Feng Zhao; Ping Huang; Rong Zeng; Robert Z. Qi; Wenjun Li; Yong Liu
• Keywords: Hyperinsulinemia; Overnutrition; Lipogenesis

Background Leptin is an adipocyte-derived hormone that plays a critical role in energy homeostasis and lipid metabolism. Overnutrition-associated obesity known to be accompanied by hyperleptinemia. However, the physiological actions of leptin metabolic responses high-fat diet (HFD) intake remain completely elucidated. Here we characterized features mice fed diets investigated impact upon lipogenic program which was found suppressed HFD feeding through proteomics approach. Results When maintained on two types for up 16 weeks, with higher fat exhibited increased body accumulation at greater pace, developing more severely impaired glucose tolerance. Notably, 4 weeks elicited onset marked hyperleptinemia, prior occurrence apparent insulin resistance hyperinsulinemia. Proteomic analysis revealed dramatically decreased expression enzymes white adipose tissue (WAT) from HFD-fed mice, including ATP-citrate lyase (ACL) fatty acid synthase (FAS). The ACL FAS liver similarly response feeding. By contrast, HFD-induced downregulation hepatic significantly attenuated receptor-deficient db/db mice. Furthermore, WAT wild type animals, intraperitoneal administration able directly suppress these enzymes, reduced triglyceride levels both serum. Conclusions These results suggest contributes adaptation overnutrition suppressing pathway represents key targeted peripheral component exerting leptin's liporegulatory actions.