Dietary Protein Restriction Increases Hepatic Leptin Receptor mRNA and Plasma Soluble Leptin Receptor in Rodents

Background: Leptin is an adipokine that regulates adipose tissue mass through membrane-anchored leptin receptor (Ob-R). Extracellular domain of Ob-R in plasma is called soluble leptin receptor (sOb-R), and is the main leptin-binding protein. This study aimed to clarify the effect of dietary protein restriction on hepatic Ob-R mRNA and plasma sOb-R levels. Methods: The effect of protein restriction on hepatic Ob-R mRNA level was examined using 5 weeks old Wistar rats fed either control diet with 20% casein (20C) or low-protein diet with 5% casein (5C) for 7 days and sacrificed after 12-h fasting or 12-h re-feeding following fasting. Effect of protein restriction on liver Ob-R and plasma sOb-R was investigated in 5 weeks old C57BL/6J mice fed 20C or 5C for 7 days. The direct effect of amino acid deprivation on Ob-R mRNA level was examined with hepatoma cells H4IIE. Results: Protein restriction increased hepatic Ob-R mRNA content more than fasting. Hepatic Ob-R mRNA level was also increased in protein restrictedmice although it did not increase in hypothalamus. Hepatic Ob-R protein was decreased, whereas plasma sOb-R was increased by protein restriction. Although plasma leptin concentration was not influenced by protein restriction, free leptin in plasma was significantly reduced. Ob-R mRNA content in H4IIE cells was not affected by amino acid deprivation in the medium. Conclusion: Dietary protein restriction increased hepatic Ob-R mRNA, resulting in increased plasma sOb-R concentration, which in turn, reduces plasma free leptin level and may modulate leptin activity.