Does Liver Fat Cause Insulin Resistance?
Is the observed association between high liver fat and reduced suppression of VLDL1 by insulin the result of fatty liver, or is fatty liver merely a consequence of hepatic insulin resistance? The existence of a causal relationship between liver fat and hepatic insulin resistance is controversial with conflicting results: (1) Fatty liver and insulin resistance may be separate manifestations of metabolic derangements, and hepatic insulin resistance may reflect inflammation rather than lipid accumulation in this tissue.111 (2) Some studies suggest that insulin resistance is an essential requirement for the accumulation of hepatocellular fat.107,112,113 It is indeed possible that hepatic steatosis results from insulin resistance because the insulin signaling pathways that drive fatty acid biosynthesis in the liver are relatively sensitive to the high levels of portal insulin flux to the liver that accompany systemic insulin resistance. (3) Several lipid intermediates (eg, ceramides, GM3 ga
