Thiazolidinedione exposure increases the expression of uncoupling protein 1 in cultured human preadipocytes.
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 (PPARgamma). 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 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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Administration of thiazolidinediones induces changes in mitochondrial content and remodeling in white adipocytes concomitantly with an improvement in insulin sensitivity.
“Administration of thiazolidinediones induces changes in mitochondrial content and remodeling in white adipocytes concomitantly with an improvement in insulin sensitivity (170, 173, 177, 190, 194 -198).”
From The role of mitochondria in the pathogenesis of type 2 diabetes (2010) · cites this paper as [196]
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“Moreover, BAT is expressed in newborn humans; adrenergic stimuli can induce UCP1 in adult humans as evident by the expression of BAT in patients with pheochromocytoma (9); and UCP1 can be induced by catecholamine (10) or thiazolidinedione (13) in human preadipocytes.”
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- Authors
- Digby, J. E., Montague, C. T., Sewter, C. P., Sanders, L., Wilkison, W. O., O'Rahilly, S., & Prins, J. B.
- Affiliations
- University of Cambridge (GB)
- Molecular Biochemistry, GlaxoWellcome,Research Triangle Park North Carolina
- Departments of Medicine and Clinical Biochemistry, University of Cambridge Cambridge, U.K.
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 1998-01-01
- Volume
- 47
- Issue
- 1
- Pages
- 138-141
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2060846519
- Cited by
- 134
- References
- 0
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 2 · 2019: 4 · 2018: 6 · 2017: 8 · 2016: 4 · 2015: 7 · 2014: 5 · 2013: 4 · 2012: 4
- FWCI
- 6.13
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Cambridge
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- thiazolidinediones, UCP1, brown adipose tissue, human preadipocytes, PPARγ, adipose tissue depots, perirenal fat, adipogenesis, insulin resistance, energy expenditure
- MeSH terms
- Uncoupling Protein 1, Rosiglitazone, Base Sequence, Carrier Proteins, Cells, Cultured, Female, Gene Expression Regulation, Humans, Hypoglycemic Agents, Ion Channels, Male, Membrane Proteins, RNA, Messenger, Stem Cells, Thiazoles, Transcription Factors, Polymerase Chain Reaction, Adipocytes, DNA Primers, Receptors, Cytoplasmic and Nuclear, Mitochondrial Proteins, Thiazolidinediones
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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