Adipokines in NASH: postprandial lipid metabolism as a link between adiponectin and liver disease

Circulating levels of four adipokines (adiponectin, TNF-, leptin, and resistin) and the
postprandial lipid and adiponectin responses to an oral fat load were assessed in 25 nonobese, non-diabetic patients with biopsy-proven nonalcoholic steatohepatitis (NASH) and
correlated with metabolic indices and liver histology. Circulating adiponectin was lower in
NASH compared with controls (5,476 344 vs. 11,548 836 ng/mL; P .00001) and on
multiple regression analysis correlated negatively with liver steatosis, necroinflammation
(OR 5.0; P .009), and fibrosis (OR 8.0; P .003).The magnitude of postprandial
lipemia was significantly higher in NASH than in controls and was related to fasting adiponectin ( 0.78; P .00003). Controls showed a significant increase in serum adiponectin in response to the fat load, whereas patients with NASH showed a slight decrease.
Postprandial free fatty acids response correlated inversely with adiponectin response in both
groups and independently predicted the severity of liver steatosis in NASH ( 0.51; P
.031). In conclusion, hypoadiponectinemia is present before overt diabetes and obesity
appear and correlates with the severity of liver histology in NASH. Impaired postprandial
lipid metabolism may be an additional mechanism linking hypoadiponectinemia and NASH
and posing a higher cardiovascular risk to these subjects. The mechanism(s) underlying these
differences are unknown, but the type of dietary fat seems to play a role. These findings may
have important pathogenetic and therapeutic implications in both liver and metabolic disease. (HEPATOLOGY 2005;42:1175-1183.)