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Acquired Obesity Increases CD68 and Tumor Necrosis Factor- and Decreases Adiponectin Gene Expression in Adipose Tissue: A Study in Monozygotic Twins

Obesity Research Unit (K.H.P., A.R.), Department of Psychiatry, and Department of Medicine (K.H.P., H.Y.-J.), Division of Diabetes, Helsinki University Central Hospital, FIN-00290 Helsinki, Finland; The Finnish Twin Cohort Study (K.H.P., J.K.), Department of Public Health, University of Helsinki, 00014 Helsinki, Finland; Department of Medicine (K.K., E.E., A.H., H.Y.-J.), Atherosclerosis Research Unit, King Gustaf V Research Institute, Karolinska Institute, SE-171 77 Stockholm, Sweden; Minerva Foundation for Medical Research (E.K., H.Y.-J.), 00290 Helsinki, Finland; and Department of Mental Health and Alcohol Research (J.K.), National Public Health Institute, 00300 Helsinki, Finland

Address all correspondence and requests for reprints to: Kirsi Pietiläinen, M.D., Ph.D., M.Sc., Obesity Research Unit, Biomedicum Helsinki, C428a, P.O. Box 700, FIN-00029 HUS, Finland. E-mail: kirsi.pietilainen{at}helsinki.fi.

Context: Both acquired and genetic factors regulate adipose tissue function.

Objective: We determined whether adipose tissue mRNA expression is regulated by obesity, independently of genetic effects, by studying monozygotic (MZ) twins.

Design: Seventeen healthy pairs of MZ twins aged 24–27 yr (body mass index 20.0–33.9 kg/m², intrapair differences in body weight 0.1–24.7 kg), were identified from the population-based FinnTwin16 cohort. Body fat percent was determined by dual-energy x-ray absorptiometry, sc and intraabdominal fat by magnetic resonance imaging, liver fat by proton spectroscopy, and insulin sensitivity by using the euglycemic insulin clamp technique. Adipocyte cell size and expression of 10 genes (real-time PCR) were determined in sc adipose tissue biopsies. Serum levels of some of the genes were measured using ELISA.

Results: Within MZ twin pairs, acquired obesity was significantly related to increased adipocyte size and increased adipose tissue mRNA expressions of leptin, TNF and the macrophage marker CD68, and decreased mRNA expressions of adiponectin and peroxisome proliferator-activated receptor-. Intrapair differences in liver fat correlated directly with those in leptin and CD68 expression. CD68 expression and serum TNF concentrations were correlated with insulin resistance.

Conclusions: Acquired obesity independent of genetic influences is able to increase expression of macrophage and inflammatory markers and decrease adiponectin expression in adipose tissue.

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