Adipokines in NASH: Postprandial Lipid Metabolism as a Link Between Adiponectin and Liver Disease *

Abstract

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

Role of APN and TNF-α in type 2 diabetes mellitus complicated by nonalcoholic fatty liver disease

“…Numerous studies have found that low APN is characteristic of fatty liver independently from IR and TNF-a (Hui et al, 2004;Musso et al, 2005a), the level of which was negatively correlated with liver steatosis, inflammatory necrosis, and fibrosis (Musso et al, 2005b). In T2DM, particularly in obese T2DM, plasma APN level also decreased significantly, which was negatively correlated with IR and hyperinsulinemia (Weyer et al, 2001).…”

Dietary and physical activity patterns in children with fatty liver

“…Most children (95%) in this cohort were overweight or obese. They displayed metabolic characteristics typical of NAFLD (Patton et al, 2006;Roberts, 2007): insulin resistance with hyperinsulinemia; dyslipidemia; hypoadipoinectinemia (Musso et al, 2005;Gilardini et al, 2006;Nakayama et al, 2009). WC, as such or expressed as waist-height ratio, was increased in all but one child.…”

Hepatic adiponectin receptors (ADIPOR) 1 and 2 mRNA and their relation to insulin resistance in obese humans

“…Specifically, adiponectin signalling alleviated or prevented NASH in mice, 33,34 and associations of hypoadiponectinaemia with fatty liver and/or NASH have been reported in humans. 35,36 Furthermore, genetic studies revealed associations of ADIPOR1/2 with IR and liver fat content, 37,38 and overexpression of ADIPOR1/2 has been shown to potentiate subeffective doses of adiponectin. 39 We therefore suggest that the increased ADIPOR1/2 mRNA expression in obese, insulin-resistant subjects represents a mechanism that may partially compensate for reduced plasma adiponectin.…”