Heterozygosity for leptin receptor (fa) accelerates hepatic triglyceride accumulation without hyperphagia in Zucker rats

Leptin, ob gene product, and its receptors are involved in the regulation of peripheral lipid and glucose metabolism. The present study sought to clarify the functional role of peripheral leptin receptors in hepatic lipid metabolism through analysis of Zucker rats (fa/fa, +/fa), as complete or partial leptin receptor insufficiency models, respectively. In Zucker fa/fa rats, calorie intake, body weight, liver weight, hepatic triglyceride content and serum insulin, triglycerides, FFA, and leptin were elevated compared to lean littermates (+/+ rats). In contrast, Zucker +/fa rats showed no remarkable changes in calorie intake, body weight and serum FFA compared with +/+ rats. Nevertheless, hepatic triglyceride content, liver weight and other serum parameters such as insulin, triglyceride and leptin were higher than in +/+ rats. In the representation of fatty acids component in the liver, there were no changes in +/fa rats relative to +/+ rats. Thus, in Zucker +/fa rats, fatty liver may develop in the absence of hyperphagia, obesity or changes in hepatic fatty acid metabolism. These results indicate that partial insufficiency of leptin receptor rather than changes in serum insulin, triglyceride and leptin may contribute to the increase in hepatic triglyceride content observed in +/fa rats.