The DOI matches its Crossref record.
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 (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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Items 101–129 of 129
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Increased susceptibility to OVX-associated metabolic dysfunction in UCP1-null mice
Clookey, S. L., Welly, R. J., Zidon, T. M., Gastecki, M. L., Woodford, M. L., Grunewald, Z. I., Winn, N. C., Eaton, D., Karasseva, N. G., Sacks, H. S., et al. (2018) · Journal of Endocrinology · doi:10.1530/joe-18-0139 · Cited by 12
Serum levels of uncoupling proteins in patients with differential insulin resistance
Pan, H., Lee, C., Chou, K.-M., Lu, S.-C., & Sun, C. (2017) · Medicine · doi:10.1097/md.0000000000008053 · Cited by 10
“5 correlated with the beneficial effects of thiazolidinedione on insulin resistance.([26]) An investigation also reported that aldosterone administration inhibited UCP 1 expression, thereby enhancing insulin resistance and the pro-inflammatory response.”
BackgroundPorter, R. K., & Andrews, J. F. (1998) · Proceedings of The Nutrition Society · doi:10.1079/pns19980065 · Cited by 10
“Recent studies on cultured human pre-adipocytes show a marked increase in UCPl in response to peroxisomal proIiferating activator receptor agonist, troglitazone (Paulik & Lenhard, 1997; Digby et al. 1998).”
BackgroundChu, D., Tao, Y., Sơn, L. H., & Le, D. (2016) · Journal of Physiology and Biochemistry · doi:10.1007/s13105-017-0567-z · Cited by 10
Jinlida Granules Reduce Obesity in db/db Mice by Activating Beige Adipocytes
Zhou, H., Wang, T., Hao, Y., et al. (2022) · BioMed Research International · doi:10.1155/2022/4483009 · Cited by 9
“Through literature search, we obtained fi ve small molecular compounds (berberine [25], thiazolidinedione [26], rhein [27], formononetin [28], and fl uvastatin sodium [29]), which can activate UCP1 as the control.”
Cited4 is a sex‐biased mediator of the antidiabetic glitazone response in adipocyte progenitors
Bayindir‐Buchhalter, I., Wolff, G., Lerch, S., Sijmonsma, T., Schuster, M., Gronych, J., Billeter, A. T., Babaei, R., Krunic, D., Ketscher, L., et al. (2018) · EMBO Molecular Medicine · doi:10.15252/emmm.201708613 · Cited by 8
Modulating the Genomic Programming of AdipocytesPreprint
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“It is well established that long-term exposure to TZDs promotes the formation of functional brown-like adipocytes in rodent and human adipocyte cultures and white adipose tissue (Digby et al. 1998; Fukui et al. 2000; Bogacka et al. 2005; Elabd et al. 2009; Ishibashi and Seale 2010; Petrovic et al. 2010; Wu et al. 2012…”
BackgroundWhite adipose tissue browning and peroxisome proliferator activated receptors in MASLD
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The autophagic regulation of rosiglitazone-promoted adipocyte browning
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Agarwal, A. K., Tunison, K., do Vale, G. D., McDonald, J. G., Li, X., Scherer, P. E., Horton, J. D., & Garg, A. (2023) · iScience · doi:10.1016/j.isci.2023.107806 · Cited by 5
Expression of human and mouse adenine nucleotide translocase (ANT) isoform genes in adipogenesis
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“A class of PPARγ-agonists, the thiazolidinediones, potently promote adipogenesis(32); and also promote development of the brown phenotype in culture.(16,21,24,33,34) However, this type of inducer of differentiation does not activate thermogenesis as such.”
Backgroundβ3-Adrenergic Receptor Agonists and Other Potential Anti-obesity Agents
Vansal, S. S. (2004) · American Journal of Pharmaceutical Education · doi:10.5688/aj680369 · Cited by 2
Thermogenic Differentiation of Human Adipocyte Precursors in Culture: A Systematic Review
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Role of PPARγ in adipocyte recruitment and thermogenesis
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Harms, M. (2015) · Scholarly Commons (University of Pennsylvania) · Cited by 1
Enhancing insulin action: From chemical elements to thiazolidinediones
Perfetti, R., & Chamie, K. (2001) · Journal of Endocrinological Investigation · doi:10.1007/bf03343858 · Cited by 1
Desai, A., Yang, Z., DeSouza, T., Yang, Q., Solivan-Rivera, J., & Corvera, S. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.08.10.607465 · Cited by 1
“…lipolysis, which produces fatty acids required for activation of UCP1 uncoupling in mitochondria [12] In addition to catecholamines, PPAR g agonists such as rosiglitazone and pioglitazone increase expression of UCP1 in adipose tissues of mice [13-15], and in primary adipocyte cultures [16-18].”
BackgroundCinti, S. (2006) · L Endocrinologo · doi:10.1007/bf03345942
The culture and differentiation of human pluripotent cells into brown and white adipocytes
Schinzel, R. T. (2012) · Universitätsbibliothek der FU Berlin Hochschulschriftenstelle u. Dokumentenserver · doi:10.17169/refubium-14513
The role of stem cells in adipose tissue remodeling.
Holden (2014) · ThinkIR: The University of Louisville's Institutional Repository (University of Louisville) · doi:10.18297/etd/1739
“UCP-1 expression has also been observed to increase with the use of thiazolidinediones (TZDs) (34).”
BackgroundUNDERSTANDING THE ROLE OF LIPOCALIN 2 AS AN IMPORTANT REGULATOR OF ENERGY METABOLISM
Zhang, Y. (2013) · University of Minnesota Digital Conservancy (University of Minnesota)
thermoregulationReview: Uncoupling proteins and
Argyropoulos, G. A., Harper, M., Nagai, N., Habuchi, H., Sugaya, N., Nakamura, M., Imamura, T., Elias, L. K., da Silva, F., de Paula, F. J., et al. (2015)
Loomis, C. A., Koss, T., & Chu, D. H. (2009) · Elsevier eBooks · doi:10.1016/b978-84-8086-390-2.50001-2
Núñez-Sánchez, J. A., Moreno-Cañadas, R., Brandimonte‐Hernández, M., Gómez‐Llorente, C., Aguilera, C. M., & Ruiz‐Ojeda, F. J. (2026) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2026.112815 · Cited by 1
Metadata
- 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 (medical) › 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
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