Non-alcoholic fatty liver and insulin resistance: a cause-effect relationship?
The role of insulin resistance in non-alcoholic fatty liver disease is suggested by laboratory data (hyperinsulinemia and decreased sensitivity to endogenous and exogenous insulin). The clinical association with features of the metabolic syndrome, particularly in the most aggressive stages of the disease, further confirms a causative role. Fat accumulation in the liver may stem either from genetic defects, primarily responsible for insulin resistance, or excessive calorie intake and visceral obesity, and is mediated by adipocytokines (leptin, adiponectin, tumour necrosis factor-alpha). Progression of fatty liver to steatohepatitis may be the result of an imbalance between pro-inflammatory and anti-inflammatory cytokines, triggering the formation of reactive oxygen species and intrahepatic lipid peroxidation. This process may also be promoted or accelerated by pro-oxidant xenobiotics or environmental factors. Insulin resistance provides a target for specific treatment of non-alcoholic fatty liver, and insulin-sensitising agents (metformin or thiazolidinediones) as well as lifestyle changes to reduce visceral adiposity are the most promising therapeutic options. Future trials need to be performed in order to test the long-term effectiveness of these treatments on the basis of clinically relevant histological outcomes.
Bugianesi
E
E
Gastroenterology Department, University of Turin, Turin, Italy.
Zannoni
C
C
Vanni
E
E
Marzocchi
R
R
Marchesini
G
G
D000273:Adipose Tissue / Q000378:metabolism; D005234:Fatty Liver / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007333:Insulin Resistance / Q000502:physiology*; D015850:Interleukin-6 / Q000502:physiology; D020738:Leptin / Q000502:physiology; D008954:Models, Biological; D045162:Thiazolidinediones / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D007004:Hypoglycemic Agents; D015850:Interleukin-6; D020738:Leptin; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha