phosphothreonine and Fatty-Liver

This study investigated the molecular effects of acylated (AG) and unacylated ghrelin (UAG) or their combination on hepatic lipogenesis pathways and DAG/PKC/JNK signaling in the livers of lean rats fed standard diet. Male rats (n = 10) were classified as control + vehicle (saline, 200 μl), AG, UAG, and AG + UAG-treated groups. All treatments were given at final doses of 200 ng/kg of for 14 days (twice/day, S.C). Administration of AG significantly enhanced circulatory levels of AG and UAG turning the normal ratio of AG/UAG from 1:2.5 to 1:1.2. However, while UAG didn't affect circulatory levels of AG, administration of UAG alone or in combination with AG resulted in AG/UAG ratios of 1:7 and 1:3, respectively. Independent of food intake nor the development of peripheral IR, AG increased hepatic DAG, TGs and CHOL contents and induced hepatic IR. Mechanism of action include 1) upregulation of mRNA and protein levels of DGAT-2 and mtGPAT-1, SREBP-1 and SCD-1, and 2) inhibition of fatty acids (FAs) oxidation mediated by inhibition of AMPK/ PPAR-α/CPT-1 axis. Consequently, AG induced membranous translocation of PKCδ and PKCε leading to activation of JNK and significant inhibition of insulin signaling under basal and insulin stimulation as evident by decreases in the phosphorylation levels of IRS (Tyr

Topics: Acylation; Animals; Blood Glucose; Body Weight; Diglycerides; Fatty Liver; Gene Expression Regulation; Ghrelin; Hepatocytes; Insulin; Insulin Resistance; JNK Mitogen-Activated Protein Kinases; Liver; Male; Phosphorylation; Phosphothreonine; Protein Kinase C; Protein Transport; Rats, Wistar; RNA, Messenger; Signal Transduction; Thinness