Ectopic fat in insulin resistance, dyslipidemia, and cardiometabolic disease

摘要

Shulman provides important information about the mechanisms by which increased storage of ectopic fat induces insulin resistance in the liver and in skeletal muscle. However, there is still limited information available on how such mechanisms affect other organs and tissues and thereby induce the development of cardiometabolic diseases. We have shown that in humans, the ectopic storage of fat in the liver, more so than skeletal muscle, is associated with impaired metabolism. The mechanisms of action involve hepatokines, proteins released from the steatotic liver. The hepatokine fetuin-A is a likely actor; its production is increased in nonalcoholic fatty liver disease, and it induces insulin resistance and subclinical inflammation in mice and humans.