Thiazolidinedione exposure increases the expression of uncoupling protein 1 in cultured human preadipocytes

Digby, JE, Montague, CT, Sewter, CP, Sanders, L, Wilkison, WO, O'Rahilly, S and Prins, JB (1998) Thiazolidinedione exposure increases the expression of uncoupling protein 1 in cultured human preadipocytes. Diabetes, 47 1: 138-141. doi:10.2337/diabetes.47.1.138

Author Digby, JE
Montague, CT
Sewter, CP
Sanders, L
Wilkison, WO
O'Rahilly, S
Prins, JB
Title Thiazolidinedione exposure increases the expression of uncoupling protein 1 in cultured human preadipocytes
Journal name Diabetes   Check publisher's open access policy
ISSN 0012-1797
Publication date 1998-01-01
Year available 1998
Sub-type Article (original research)
DOI 10.2337/diabetes.47.1.138
Open Access Status
Volume 47
Issue 1
Start page 138
End page 141
Total pages 4
Place of publication ALEXANDRIA
Language eng
Abstract Thiazolidinediones (TZDs) are a novel class of insulin-sensitizing agents used in the treatment of NIDDM and are potent agonists for the nuclear hormone receptor peroxisome proliferator-activated receptor gamma (PPAR gamma). 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 vehicle-treated cells. When exposed to BRL 49653 for 5 days, preadipocytes from the human perirenal depot accumulated lipid, and a proportion of cells showed clear mitochondrial straining 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.
Keyword Brown Adipose-Tissue
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
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