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1 Department of Endocrinology and Metabolism C, Aarhus Amtssygehus, Aarhus University Hospital and Faculty of Health Sciences, DK-8000 Aarhus C, Denmark
2 Research Department of Human Nutrition, Centre for Advanced Food Research, The Royal Veterinary and Agricultural University, DK-1958 Frederiksberg C, Denmark
* To whom correspondence should be addressed. E-mail: jmb{at}mail-online.dk.
Adiponectin is a newly discovered adipose tissue-specific protein, abundantly present in the circulation, and suggested to be involved in regulation of insulin sensitivity and development of atherosclerosis. The aim of the present study was to investigate factors that may be involved in the regulation of adiponectin. Since cytokines have been suggested to regulate the production of adiponectin, we investigated the interaction between adiponectin and three adipose tissue-derived cytokines: interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-
(TNF-), in vivo and in vitro. The study was divided in three sub-studies: 1) Adiponectin levels in plasma and adiponectin mRNA levels in adipose tissue-biopsies from six obese subjects (mean BMI: 39.7 ± 0.6 kg/m2) before and after weight loss. 2) Plasma levels of adiponectin in nineteen obese men (mean BMI: 38.7 ± 0.7 kg/m2) before and after weight loss. Ten lean men (mean BMI: 23.4 ± 0.4 kg/m2) were included for comparison. 3) The direct effect of IL-6, IL-8 and TNF- on the expression of adiponectin in vitro in whole adipose tissue cultures. Results: 1) Weight loss resulted in a 51 % (p < 0.05) increase in plasma adiponectin levels, paralleled in adipose tissue-biopsies by a 45 % (p < 0.05) increase in adiponectin mRNA levels. 2) Plasma adiponectin was 53 % (p < 0.01) higher in lean men as compared with obese. Before and after weight loss plasma adiponectin was inversely correlated with measures of adiposity, insulin sensitivity and the level of cytokines investigated, particular IL-6. 3) In vitro adiponectin mRNA levels was decreased when incubating with TNF- (p < 0.01) and IL-6 plus its soluble receptor (p < 0.05). The inverse relationship between plasma levels of adiponectin and cytokines in vivo and the cytokine-induced reduction in adiponectin mRNA level in vitro suggests that endogenous cytokines may inhibit adiponectin which could be of importance for the association between cytokines (e.g. IL-6) and insulin resistance and atherosclerosis.
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