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Total and High Molecular Weight But Not Trimeric or Hexameric Forms of Adiponectin Correlate with Markers of the Metabolic Syndrome and Liver Injury in Thai Subjects

Division of Endocrinology (R.R., A.H.) and Department of Nutritional Sciences (A.H.), University of Toronto, Toronto, Ontario, Canada M5S 2E4; Leadership Sinai Centre for Diabetes (R.R.), Mount Sinai Hospital, Toronto, Canada M5G 1X5; Department of Tropical Nutrition and Food Science (R.T.), Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand; American Laboratory Products Company (ALPCO Diagnostics) (C.S.), Salem, New Hampshire 03079; and Department of Biology (Y.L., G.S.), York University, Toronto, Ontario, Canada M3J 1P3

Address all correspondence and requests for reprints to: Gary Sweeney, Department of Biology, York University Toronto, M3J 1P3, Ontario, Canada. E-mail: gsweeney{at}yorku.ca.

Context/Objective: Decreased total adiponectin has been associated with metabolic disorders, including obesity, diabetes, fatty liver, and the metabolic syndrome. Although circulating adiponectin is composed of trimers, hexamers, and high molecular weight (HMW) multimers, there has been limited study of the specific metabolic correlates of these isoforms in humans. Thus, our objective was to evaluate the associations of these adiponectin isoforms with metabolic and anthropometric parameters.

Design/Participants/Setting: A total of 53 diabetic and 68 nondiabetic subjects attending outpatient clinics underwent cross-sectional metabolic characterization. Circulating levels of HMW, hexameric, and trimeric adiponectin were measured using a multimeric adiponectin ELISA based upon selective protease-mediated digestion.

Results: On Spearman univariate analysis, both total and HMW adiponectin levels were inversely associated with body mass index, fasting glucose, homeostasis model of assessment of insulin resistance, triglycerides, and alanine aminotransferase (ALT) (all |r| 0.22; P < 0.05), with the HMW isoform also positively correlated with high-density lipoprotein cholesterol (r = 0.19; P = 0.036). In contrast, hexameric and trimeric adiponectin were significantly associated with only body mass index (r = –0.23; P = 0.0102) and mid-upper arm circumference (r = 0.21; P = 0.039), respectively. On separate forward stepwise multiple linear regression analyses, fasting glucose and ALT emerged as independent, negative covariates of both total and HMW adiponectin, whereas no independent covariates of hexameric and trimeric adiponectin were identified. Furthermore, after adjustment for age, gender, and diabetes, mean ALT was highest in subjects in the lowest tertile of HMW adiponectin, followed in turn by the middle and highest tertiles, respectively (trend P = 0.028).

Conclusions: HMW adiponectin, but not hexameric or trimeric, tracks with the metabolic correlates of total adiponectin. Furthermore, an independent inverse association exists between ALT and HMW adiponectin.