Clinical Science (2010) 118, 397-400 - Commentary

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Clinical Science (2010) 118, (397–400) (Printed in Great Britain)

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Paper by A. Piguet et al.

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Commentary

Hypoxia and non-alcoholic fatty liver disease

Christopher D. Byrne

Department of Endocrinology and Metabolism, The Institute of Developmental Sciences, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, U.K.

Key words: β-oxidation, fatty liver, lipogenesis, non-alcoholic steatohepatitis (NASH), peroxisome-proliferator-activated receptor (PPAR), phosphatase and tensin homologue deleted on chromosome 10 (PTEN), sterol-regulatory-element-binding protein-1c (SREBP-1c).

Abbreviations: CYP2E1, cytochrome P450 2E1; HIF-2α, hypoxia-induced factor-2α; mTOR, mammalian target of rapamycin; NAFLD, non-alcoholic fatty liver disease; NASH, non-alcoholic steatohepatitis; NEFA, non-esterified fatty acid (‘free fatty acid’); NF-κB, nuclear factor κB; PI3K, phosphoinositide 3-kinase; PPAR-γ, peroxisome-proliferator-activated receptor-γ; PTEN, phosphatase and tensin homologue deleted on chromosome 10; SREBP-1c, sterol-regulatory-element-binding protein-1c.

Correspondence: Professor Christopher D. Byrne (email cdtb@southampton.ac.uk).

NAFLD (non-alcoholic fatty liver disease) represents a spectrum of fatty liver diseases associated with an increased risk of Type 2 diabetes and cardiovascular disease. The spectrum of fatty liver diseases comprises simple steatosis, steatosis with inflammation [i.e. NASH (non-alcoholic steatohepatitis)], fatty liver disease with inflammation and fibrosis (severe NASH) and cirrhosis. The molecular mechanisms contributing to NASH are the subject of considerable investigation, as a better understanding of the pathogenesis of NASH will lead to novel therapies for a condition that hitherto remains difficult to treat. In the present issue of Clinical Science, Piguet and co-workers have investigated the effects of hypoxia in the PTEN (phosphatase and tensin homologue deleted on chromosome 10)-deficient mouse, a mouse model that develops NAFLD. The authors show that a short period (7 days) of exposure to hypoxia aggravates the NAFLD phenotype, causing changes in the liver that are in keeping with NASH with increased lipogenesis and inflammation.