Intrahepatic vascular changes in non-alcoholic fatty liver disease: Potential role of insulin-resistance and endothelial dysfunction

World J Gastroenterol. 2017 Oct 7;23(37):6777-6787. doi: 10.3748/wjg.v23.i37.6777.

Abstract

Metabolic syndrome is a cluster of several clinical conditions characterized by insulin-resistance and high cardiovascular risk. Non-alcoholic fatty liver disease is the liver expression of the metabolic syndrome, and insulin resistance can be a frequent comorbidity in several chronic liver diseases, in particular hepatitis C virus infection and/or cirrhosis. Several studies have demonstrated that insulin action is not only relevant for glucose control, but also for vascular homeostasis. Insulin regulates nitric oxide production, which mediates to a large degree the vasodilating, anti-inflammatory and antithrombotic properties of a healthy endothelium, guaranteeing organ perfusion. The effects of insulin on the liver microvasculature and the effects of IR on sinusoidal endothelial cells have been studied in animal models of non-alcoholic fatty liver disease. The hypotheses derived from these studies and the potential translation of these results into humans are critically discussed in this review.

Keywords: Endothelial dysfunction; Insulin resistance; Metabolic syndrome; Non-alcoholic fatty liver disease.

Publication types

  • Review

MeSH terms

  • Animals
  • Disease Models, Animal
  • Endothelial Cells / enzymology
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / enzymology
  • Endothelium, Vascular / physiopathology*
  • Humans
  • Insulin / metabolism*
  • Liver / blood supply
  • Liver / pathology
  • Metabolic Syndrome / complications
  • Metabolic Syndrome / pathology*
  • Microvessels / cytology
  • Microvessels / physiopathology*
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase / metabolism
  • Non-alcoholic Fatty Liver Disease / etiology
  • Non-alcoholic Fatty Liver Disease / pathology*
  • Oxidative Stress
  • Vasodilation

Substances

  • Insulin
  • Nitric Oxide
  • Nitric Oxide Synthase