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Adipose Triglyceride Lipase and Hormone-Sensitive Lipase Protein Expression Is Decreased in the Obese Insulin-Resistant State

Department of Human Biology (J.W.E.J., E.S., W.H.M.S., G.B.H., E.E.B.), Nutrition and Toxicology Research Institute Maastricht, Maastricht University, 6200 MD Maastricht, The Netherlands; Obesity Research Unit (D.L., C.V.), Institut National de la Santé et de la Recherche Médicale, Unité 586, F-31432 Toulouse, France; Paul Sabatier University (D.L., C.V.), Louis Bugnard Institute, Institut Fédératif de Recherche 31, F-31432 Toulouse, France; Centre Hospitalier Universitaire de Toulouse (D.L.), Biochemistry Laboratory, Biology Institute of Purpan, F-31059 Toulouse, France; Department of Experimental Medical Science (C.H.), Division of Diabetes, Metabolism, and Endocrinology, Lund University, SE-221 00 Lund, Sweden; and Department of Medicine (P.A.), Karolinska Institutet, Karolinska University Hospital, Huddinge, SE-141 86 Stockholm, Sweden

Address all correspondence and requests for reprints to: Dr. Johan W. E. Jocken, Department of Human Biology, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands. E-mail: j.jocken{at}hb.unimaas.nl.

Aim/Hypothesis: Obesity is associated with increased triacylglycerol (TAG) storage in adipose tissue and insulin resistance. The mobilization of stored TAG is mediated by hormone-sensitive lipase (HSL) and the recently discovered adipose triglyceride lipase (ATGL). The aim of the present study was to examine whether ATGL and HSL mRNA and protein expression are altered in insulin-resistant conditions. In addition, we investigated whether a possible impaired expression could be reversed by a period of weight reduction.

Methods: Adipose tissue biopsies were taken from obese subjects (n = 44) with a wide range of insulin resistance, before and just after a 10-wk hypocaloric diet. ATGL and HSL protein and mRNA expression was determined by Western blot and quantitative RT-PCR, respectively.

Results: Fasting insulin levels and the degree of insulin resistance (using the homeostasis model assessment index for insulin resistance) were negatively correlated with ATGL and HSL protein expression, independent of age, gender, fat cell size, and body composition. Both mRNA and protein levels of ATGL and HSL were reduced in insulin-resistant compared with insulin-sensitive subjects (P < 0.05). Weight reduction significantly decreased ATGL and HSL mRNA and protein expression. A positive correlation between the decrease in leptin and the decrease in ATGL protein level after weight reduction was observed. Finally, ATGL and HSL mRNA and protein levels seem to be highly correlated, indicating a tight coregulation and transcriptional control.

Conclusions: In obese subjects, insulin resistance and hyperinsulinemia are strongly associated with ATGL and HSL mRNA and protein expression, independent of fat mass. Data on weight reduction indicated that also other factors (e.g. leptin) relate to ATGL and HSL protein expression.

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