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Depot-related and thiazolidinedione-responsive expression of uncoupling protein 2 (UCP2) in human adipocytes

International Journal of Obesity volume 24, pages 585–592 (2000)Cite this article

Abstract

OBJECTIVES: Uncoupling protein 2 (UCP2) is a recently described homologue of the uncoupling protein of brown adipocytes (UCP1), which is expressed at high levels in human white adipose tissue. Studies were undertaken (1) to establish whether the expression of UCP2 mRNA varies in a depot-related manner in isolated human adipocytes, (2) to determine whether thiazolidinedione exposure influences the expression of UCP2 mRNA in cultured human pre-adipocytes, and (3) to determine whether human UCP2 is targeted to mitochondria when transfected into mammalian cells.

SUBJECTS: Abdominal subcutaneous and omental adipose tissue biopsies were obtained from adult patients undergoing elective intra-abdominal surgical procedures.

MEASUREMENTS: A competitive reverse transcriptase-polymerase chain reaction (RT-PCR) was used to quantify UCP2 mRNA expression in human omental and subcutaneous adipocytes, and in cultured human preadipocytes differentiated in vitro using the thiazolidinedione, BRL49653. Chinese hamster ovary cells were transfected with a vector expressing human UCP2, and its cellular localization was determined by confocal immunofluorescence microscopy.

RESULTS: Adipocytes isolated from human omentum consistently expressed more UCP2 mRNA than did subcutaneous adipocytes from the same subjects (mean fold difference 2.92±0.44 P<0.001, n=11) with no effect of gender or body mass index being seen. BRL49653 treatment of subcutaneously, but not omentally, derived preadipocytes stimulated expression of UCP2 mRNA (5.1±1.1 fold). Transfected human UCP2 was detected exclusively in mitochondria of CHO cells.

CONCLUSIONS: Increased expression of UCP2 in human omental adipose tissue relative to subcutaneous adipose tissue is related to the expression levels in adipocytes per se, a finding which may relate to the particular functional attributes of this sub-population of adipocytes. Furthermore, BRL 49653 has site-specific effects of on the expression of UCP2 in human preadipocytes, a finding which may be relevant to the therapeutic effects of such compounds. Finally we present evidence for the mitochondrial localisation of human UCP2.

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Acknowledgements

This work was supported by a grant from Glaxo Wellcome (JD, SOR). SOR, JBP, JPW and VEFC are supported by the Wellcome Trust and CS by the British Diabetic Association. We would like to thank Professor Ken Siddle for his help in the development of the anti-UCP2 antibody. The assistance of members of the Departments of Surgery and Obstetrics and Gynaecology of Addenbrooke's Hospital and the University of Cambridge, in particular Peter Friend, Neville Jamieson, John Williamson and Michael Bright is also greatly appreciated.

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Author notes

  1. JE Digby

    Present address: Diabetes Research Group, School of Health Sciences, University of Wolverhampton, UK

  2. JE Digby and VEF Crowley: These authors contributed equally to the work presented in this paper.

Authors and Affiliations

  1. Departments of Medicine and Clinical Biochemistry, University of Cambridge, Cambridge, UK

    JE Digby, VEF Crowley, CP Sewter, JP Whitehead, JB Prins & S O'Rahilly

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Correspondence to S O'Rahilly.

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Digby, J., Crowley, V., Sewter, C. et al. Depot-related and thiazolidinedione-responsive expression of uncoupling protein 2 (UCP2) in human adipocytes. Int J Obes 24, 585–592 (2000). https://doi.org/10.1038/sj.ijo.0801201

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