Thiazolidinediones (TZDs) are a novel class of insulinsensitizing agents used in the treatment of NIDDM and are potent agonists for the nuclear hormone receptor peroxisome proliferator-activated receptor γ (PPARγ). The thiazolidinedione BRL 49653 has been shown to promote the differentiation of the HIB-1B brown preadipocyte cell line and to increase rat interscapular brown adipose tissue (BAT) mass. Given the importance of brown fat in the control of energy metabolism in rodents, this may represent an important therapeutic effect of this class of compound. To date, however, no studies examining the effects of TZDs on human brown fat have been reported. In the present study, we have measured uncoupling protein 1 (UCP-1) mRNA, a specific marker for BAT, in isolated adipocytes and subcultured preadipocytes prepared from different adult human adipose tissue depots. Consistent with previous studies of adult human whole adipose tissue, UCP-1 mRNA was detectable in isolated human adipocytes prepared from all depots studied with a rank order of perirenal, omental, and subcutaneous. BRL 49653 treatment of subcultured human pre-adipocytes prepared from all depots resulted in increased levels of UCP-1 mRNA, compared with those of the vehicletreatedcells. When exposed to BRL 49653 for 5 days, preadipocytes from the human perirenal depot accumulated lipid, and a proportion of cells showed clear mitochondrial staining for UCP-1 protein by confocal microscopy. Thus, cells of the brown fat lineage were detectable in all human adipose depots studied, and cultured human pre-adipocytes, particularly from the perirenal depot, showed a marked increase in UCP-1 expression in response to thiazolidinediones. Given the role of brown adipocytes in the enhancement of energy expenditure, promotion of brown fat adipogenesis by thiazolidinediones could contribute to the beneficial effects of these drugs on insulin resistance in humans.
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January 01 1998
Thiazolidinedione Exposure Increases the Expression of Uncoupling Protein 1 in Cultured Human Preadipocytes
Janet E Digby;
Janet E Digby
Departments of Medicine and Clinical Biochemistry, University of Cambridge
Cambridge, U.K.
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Carl T Montague;
Carl T Montague
Departments of Medicine and Clinical Biochemistry, University of Cambridge
Cambridge, U.K.
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Ciaran P Sewter;
Ciaran P Sewter
Departments of Medicine and Clinical Biochemistry, University of Cambridge
Cambridge, U.K.
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Louise Sanders;
Louise Sanders
Departments of Medicine and Clinical Biochemistry, University of Cambridge
Cambridge, U.K.
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William O Wilkison;
William O Wilkison
Molecular Biochemistry, GlaxoWellcome,Research Triangle Park
North Carolina
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Stephen O'Rahilly;
Stephen O'Rahilly
Departments of Medicine and Clinical Biochemistry, University of Cambridge
Cambridge, U.K.
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Johannes B Prins
Johannes B Prins
Departments of Medicine and Clinical Biochemistry, University of Cambridge
Cambridge, U.K.
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Address correspondence and reprint requests to J.E. Digby, Department of Clinical Biochemistry, University of Cambridge, Level 4, Addenbrooke's Hospital, Hill's Road, Cambridge CB2 2QR, U.K. E-mail: [email protected]
Diabetes 1998;47(1):138–141
Article history
Received:
September 08 1997
Revision Received:
October 08 1998
Accepted:
October 08 1998
PubMed:
9421389
Citation
Janet E Digby, Carl T Montague, Ciaran P Sewter, Louise Sanders, William O Wilkison, Stephen O'Rahilly, Johannes B Prins; Thiazolidinedione Exposure Increases the Expression of Uncoupling Protein 1 in Cultured Human Preadipocytes. Diabetes 1 January 1998; 47 (1): 138–141. https://doi.org/10.2337/diab.47.1.138
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