Is adipose tissue lipolysis always an adaptive response to starvation?: implications for non-alcoholic fatty liver disease.
The physiological response to starvation involves increased muscle proteolysis and adipose tissue lipolysis that supply amino acids and non-esterified fatty acids ('free fatty acids') for gluconeogenesis, oxidation and ketogenesis. In the present issue of Clinical Science, Moller and co-workers show that, in humans, IHL (intrahepatic lipid) content, measured using (1)H-magnetic resonance spectroscopy, increases following 36 h of fasting, with a direct association with plasma levels of 3-hydroxybutyrate. The observation raises interesting questions as to how IHL levels increase in a situation of increased mitochondrial fatty acid oxidation and ketogenesis. Possible mechanisms for increased IHLs include reduced apoB-100 (apolipoprotein B-100) production and hepatic lipid export, and/or impaired mitochondrial function resulting from increased oxidative stress, with diversion of fatty acids for esterification. The accumulation of IHL during prolonged fasting may, therefore, reflect a maladaptive response to increased non-esterified fatty acid delivery to the liver that unmasks a subtle defect in mitochondrial function. This could have implications for the pathogenesis of the common human disorder of non-alcoholic fatty liver disease. The accumulation of IHLs observed with prolonged fasting may also explain exacerbations of steatohepatitis seen sometimes with rapid weight loss, anorexia nervosa and parenteral nutrition. The findings also suggest caution against promoting excessive ketogenesis with weight-loss regimens.
Gan
Seng Khee
SK
Metabolic Research Centre, School of Medicine and Pharmacology, Royal Perth Hospital, University of Western Australia, GPO Box X2213, Perth, WA 6847, Australia.
Watts
Gerald F
GF
D000273:Adipose Tissue / Q000378:metabolism*; D005234:Fatty Liver / Q000378:metabolism*; D006801:Humans; D008066:Lipolysis; D008099:Liver / Q000378:metabolism; D013217:Starvation / Q000378:metabolism*