Dietary protein restriction increases hepatic leptin receptor mRNA and plasma soluble leptin receptor in male rodents

• Published in: PloS one 2019-07, Vol.14 (7), p.e0219603-e0219603
• Main Authors: Yamada, Riho, Odamaki, Shizuka, Araki, Masaya, Watanabe, Tasuku, Matsuo, Keigo, Uchida, Kaito, Kato, Taku, Ozaki-Masuzawa, Yori, Takenaka, Asako
• Format: Article
• Language: English
• Subjects: Adipose tissue; Adipose Tissue - metabolism; Agriculture; Amino acids; Animal Feed; Animals; Biology and Life Sciences; Body fat; Cell Line, Tumor; Cell membranes; Deoxyribonucleic acid; Deprivation; Diet; Diet, Protein-Restricted; Dietary Proteins; Dietary restrictions; DNA; DNA chips; DNA microarrays; Endocrinology; Enzyme-linked immunosorbent assay; Fasting; Female; Fibroblast Growth Factors - genetics; Fibroblast Growth Factors - metabolism; Food; Food availability; Food consumption; Gene expression; Genetic research; Growth factors; Health aspects; Hepatocellular carcinoma; Hepatoma; Hypothalamus; Hypothalamus - metabolism; Insulin; Kinases; Laboratory animals; Laboratory testing; Leptin; Leptin - metabolism; Lipid Metabolism; Lipids; Liver; Liver - metabolism; Low protein diet; Male; Malnutrition; Medicine and Health Sciences; Messenger RNA; Metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; mRNA; Nervous system; Nutrient deficiency; Nutrition research; Oligonucleotide Array Sequence Analysis; Protein binding; Proteins; Rats; Rats, Wistar; Receptors, Leptin - blood; Receptors, Leptin - metabolism; RNA; RNA, Messenger - metabolism; Rodents; Signal transduction; Studies
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0219603

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. Based on a previous DNA microarray analysis that showed induction of hepatic Ob-R mRNA in low-protein diet-fed mice, this study aimed to clarify the effect of dietary protein restriction on hepatic Ob-R mRNA and plasma sOb-R levels. First, the effect of protein restriction on hepatic Ob-R mRNA level was examined together with fasting and food restriction using male rats as common experimental model for nutritional research. Hepatic Ob-R mRNA level was increased by feeding low-protein diet for 7 d, although not significantly influenced by 12-h fasting and sixty percent restriction in food consumption. Then, effect of protein restriction on liver Ob-R and plasma sOb-R was investigated using male mice because specific sOb-R ELISA was more available for mice. Hepatic Ob-R mRNA level was also increased in protein restricted-mice although it did not increase in hypothalamus. Hepatic Ob-R protein was decreased, whereas plasma sOb-R was increased by protein restriction. Because the concentration of sOb-R increased without changing plasma leptin concentration, free leptin in plasma was significantly reduced. The direct effect of amino acid deprivation on Ob-R mRNA level was not observed in rat hepatoma cells H4IIE cultured in amino acid deprived medium. In 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.