ADIPOKINES AND NONALCOHOLIC FATTY LIVER DISEASE

Adipokines secreted by adipose tissue exert powerful regulatory effects on metabolism and energy balance. The contribution of various fat depots to circulating adipokine concentrations has not been clarified. Moreover, it is unknown whether these adipokines play a role in hepatic steatosis (ST) or progression to portal fibrosis and non-alcoholic steatohepatitis (PT/NASH). The purpose of this study was to explore the relationship between adipokines produced in omental (OM) and subcutaneous (SQ) fat with circulating concentrations, and to examine whether adipokines determine which patients with ST develop PT/NASH. We studied 20 females undergoing bariatric surgery (BMI 48 ± 7 kg/m2; age 40 ± 4 yr) categorized as ST or PF/NASH by liver biopsy. In serum and in OM and SQ fat samples, we quantified the adipokines leptin, resistin, MCP-1, and adiponectin by ELISA. In serum, we also measured high molecular weight (HMW) and low MW (LMW) adiponectin multimers by immunoblot, since we reported that HMW adiponectin was correlated with insulin sensitivity and reduced risk of Metabolic Syndrome. In comparing ST and PT/NASH, there were no differences in serum leptin, resistin, MCP-1, total adiponectin, and HMW and LMW adiponectin. In adipose tissues, OM adiponectin was higher in PF/NASH compared with ST (102.1 ± 8.7 vs. 82.5 ± 19.7 ng/mL; P < 0.05), while SQ adiponectin and tissue leptin levels did not differ between subgroups. OM adiponectin was also correlated with serum HMW adiponectin (r = 0.67, P < 0.05) but not LMW; in contrast, SQ adiponectin did not correlate with either serum HMW or LMW. In conclusion: 1) Serum levels of leptin, resistin, MCP-1, adiponectin, and adiponectin multimers were similar in ST and PT/NASH patients. 2) PT/NASH patients had higher OM adiponectin. 3) OM but not SQ adiponectin was highly correlated with serum HMW, the multimer associated with insulin sensitivity. The data suggest that factors intrinsic to liver, rather than secreted adipokines, determine which patients with hepatic steatosis progress to PT/NASH.