Elevated TCA cycle function in the pathology of diet-induced hepatic insulin resistance and fatty liver

Quantitative analysis of the murine lipid droplet-associated proteome during diet-induced hepatic steatosis

“…In support of this data, ACADVL, ACSL1, MGLL, and CPT2 were also found in higher abundance on hepatic LDs in human subjects with NAFLD, suggesting that these proteins are conserved in models of NAFLD ( 14 ). Taken together, these data are consistent with more recent studies showing that fatty acid oxidation is upregulated in models of hepatic steatosis (58)(59)(60). Recent studies in nonhepatocyte cell lines suggest that LD-mitochondria interactions are important for oxidation of hydrolyzed fatty acids ( 61 ).…”

A high-fat diet suppresses de novo lipogenesis and desaturation but not elongation and triglyceride synthesis in mice

“…In previous studies, BDF1 mice fed a 64% HFD became insulin resistant by 8 weeks and had fed plasma glucose levels of 335 mg/dl after 14 weeks on the diet ( 27 ). Here we found that a 60% HFD caused profound hyperinsulinemia but mild hyperglycemia and was overall consistent with our experience using C57BL/6 mice on this diet ( 47 ). The HFD caused fat accumulation in liver, but FA synthesis (i.e., DNL) was markedly decreased.…”

Protein kinase STK25 controls lipid partitioning in hepatocytes and correlates with liver fat content in humans

“…It is generally accepted that mitochondrial β-oxidation plays an important role in liver steatosis and hepatic insulin resistance, although the nature of this role is still under debate. Increased hepatic mitochondrial oxidation has been observed in patients and rodents with fatty liver [23,24], which likely reflects a metabolic adaptation to elevated lipid burden to limit further fat accumulation. Indeed, the development of fatty liver and hepatic insulin resistance in response to high-fat feeding in rats can be prevented by increasing mitochondrial β-oxidation [25][26][27][28].…”