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Beyond insulin resistance in NASH: TNF‐α or adiponectin?
Author(s) -
Hui Jason M.,
Hodge Alex,
Farrell Geoffrey C.,
Kench James G.,
Kriketos Adamandia,
George Jacob
Publication year - 2004
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.20280
Subject(s) - adiponectin , insulin resistance , medicine , endocrinology , steatosis , steatohepatitis , fatty liver , nonalcoholic fatty liver disease , proinflammatory cytokine , insulin , inflammation , disease
Adiponectin has antilipogenic and anti‐inflammatory effects, while tumor necrosis factor α (TNF‐α) reduces insulin sensitivity and has proinflammatory effects. We examined (1) the extent to which hypoadiponectinemia and TNF‐α activation are features of nonalcoholic steatohepatitis (NASH) and (2) whether serum levels of these markers correlate with the severity of histological changes in 109 subjects with nonalcoholic fatty liver disease (NAFLD), including 80 with NASH and 29 with simple steatosis. By multivariate analysis, subjects with NASH had reduced adiponectin level and increased TNF‐α and soluble TNF receptor 2 (sTNFR2)—but not leptin levels, compared with controls matched by age, sex, and body mass index; these differences were independent of the increased insulin resistance (by homeostasis model [HOMA‐IR]) in NASH. When compared with simple steatosis, NASH was associated with lower adiponectin levels and higher HOMA‐IR, but there were no significant differences in the levels of TNF‐α and sTNFR2. The majority of subjects with steatohepatitis (77%) had adiponectin levels less than 10 μg/mL and HOMA‐IR greater than 3 units, but only 33% of those with pure steatosis had these findings. HOMA‐IR and low serum adiponectin were also independently associated with increased grades of hepatic necroinflammation. In conclusion , hypoadiponectinemia is a feature of NASH independent of insulin resistance. Reduced adiponectin level is associated with more extensive necroinflammation and may contribute to the development of necroinflammatory forms of NAFLD. (H EPATOLOGY 2004;40:46–54.)