Diurnal regulation of oxidative phosphorylation restricts hepatocyte proliferation and inflammation

• DOI: 10.1016/j.celrep.2021.109659
• Publication Date: 2021-09-07T14:30:53Z
• Authors: Xiaojie Bai; Yilie Liao; Fangfang Sun; Xia Xiao; Suneng Fu
• Keywords: Inflammation; Liver Cirrhosis; 0301 basic medicine; Mice, Obese; Oxidative Phosphorylation; Fatty Liver; Mice; 03 medical and health sciences; Liver; Hepatocytes; Animals; Obesity; Energy Metabolism; Cell Proliferation

The principles guiding the diurnal organization of biological pathways remain to be fully elucidated. Here, we perturb hepatic transcriptome through nutrient regulators (high-fat diet and mTOR signaling components) identify enduring properties pathway organization. Temporal separation counter-regulation between energy metabolism inflammation/proliferation emerge as persistent features across animal models, network analysis identifies G0s2 Rgs16 genes potential mediators at metabolism-inflammation interface. Mechanistically, are sequentially induced during light phase, promoting amino acid oxidation suppressing overall mitochondrial respiration. In their absence, sphingolipids diacylglycerides accumulate, accompanied by inflammation hepatocyte proliferation. Notably, expression is further in obese mouse livers, silencing accentuates fibrosis. Therefore, regulation alleviates inflammatory proliferative stresses under physiological pathological conditions.