Leptin acts as a metabolic regulator of Angptl6 expression

Abstract

Leptin, an adipocyte‐secreted protein, is one of the crucial regulators of food intake and energy expenditure. Circulating leptin concentration is correlated with energy intake and body fatness in rodents and humans. Recently, it has been known that some angiopoietin‐like proteins (Angptls) regulate lipid, glucose and energy metabolism. We examined the effect of leptin on the level of some Angptls using high‐fat diet and hyperleptinemia model. C57BL/6 mice were fed a HF diet or normal chow for the periods of 12 weeks.HF diet caused obesity, elevation of serum transaminase levels, and hyperlipidemia. And also HF diet induced an impaired glucose tolerance (IGT). Plasma concentration of leptin was approximately increased 4‐fold; adiponectin and RBP4 level were also increased in HF diet group. Plasma Angptl3 concentration of HF diet mice was lower than that of control mice. Angptl4 was decreased in liver, but no difference in epididyimal fat. Quantitative real‐time PCR analysis revealed that the mRNA expression level of Angptl6/AGF in liver was significantly increased in HF diet group. In leptin‐treated mice, food intake and body weight were decreased time‐dependently. Blood level of fasting glucose and triglycerides were decreased in leptin‐injected mice. Serum Angptl3 concentration of leptin‐treated mice was lower than that of control mice. Quantitative real‐time PCR analysis revealed that the mRNA expression level of Angptl3 and Angptl4 in liver were decreased, Angptl6/AGF was significantly increased in liver and epididymal fat in leptin‐treated mice.In conclusion, Angptl3, 4 were down‐regulated and Angptl6/AGF was up‐regulated by HF diet model and leptin injection mice. It could be suggested that leptin is an important regulator of Angptl6/AGF expression in hyperleptinemia.