Multilocular fat cells in WAT of CL-316243-treated rats derive directly from white adipocytes
Abstract
Multilocular, mitochondria-rich adipocytes appear in white adipose tissue (WAT) of rats treated with the beta3-adrenoceptor agonist, CL-316243 (CL). Objectives were to determine whether these multilocular adipocytes derived from cells that already existed in the WAT or from proliferation of precursor cells and whether new mitochondria contained in them were typical brown adipocyte mitochondria. Use of 5-bromodeoxyuridine to identify cells that had undergone mitosis during the CL treatment showed that most multilocular cells derived from cells already present in the WAT. Morphological techniques showed that at least a subpopulation of unilocular adipocytes underwent conversion to multilocular mitochondria-rich adipocytes. A small proportion of multilocular adipocytes ( approximately 8%) was positive for UCP1 by immunohistochemistry. Biochemical techniques showed that mitochondrial protein recovered from WAT increased 10-fold and protein isolated from brown adipose tissue (BAT) doubled in CL-treated rats. Stained gels showed a different protein composition of new mitochondria isolated from WAT from that of mitochondria isolated from BAT. Western blotting showed new mitochondria in WAT to contain both UCP1, but at a much lower concentration than in BAT mitochondria, and UCP3, at a higher concentration than that in BAT mitochondria. We hypothesize that multilocular adipocytes present at 7 days of CL treatment have two origins. First, most come from convertible unilocular adipocytes that become multilocular and make many mitochondria that contain UCP3. Second, some come from a cell that gives rise to more typical brown adipocytes that express UCP1.
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Higher mitochondrial density and even UCP1 can be induced in response to pharmacological or genetic alterations of white adipocytes, suggesting that white adipose tissue could potentially be induced to acquire more oxidative metabolic phenotypes, promoting increased fuel consumption and thus energy expenditure.
“Higher mitochondrial density and even UCP1 can be induced in response to pharmacological or genetic alterations of white adipocytes (170 -177), suggesting that white adipose tissue could potentially be induced to acquire more oxidative metabolic phenotypes, promoting increased fuel consumption and thus energy expenditure.”
From The role of mitochondria in the pathogenesis of type 2 diabetes (2010) · cites this paper as [171]
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- Authors
- Himms-Hagen, J., Melnyk, A., Zingaretti, M. C., Ceresi, E., Barbatelli, G., & Cinti, S.
- Affiliations
- Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa K1H 8M5, Canada; and
- University of Ottawa (CA)
- Institute of Normal Human Morphology-Anatomy, Faculty of Medicine, University of Ancona, 60020 Ancona, Italy
- ORCID
- Venue
- American Journal of Physiology-Cell Physiology
- Publisher
- American Physiological Society
- Published
- 2000-09-01
- Volume
- 279
- Issue
- 3
- Pages
- C670-C681
- ISSN
- 0363-6143 (ISSN-L)
- 1522-1563
- OpenAlex
- W2136040666
- Cited by
- 593
- References
- 42
- Citations by year
- 2026: 6 · 2025: 14 · 2024: 10 · 2023: 13 · 2022: 31 · 2021: 37 · 2020: 38 · 2019: 31 · 2018: 39 · 2017: 42 · 2016: 36 · 2015: 41 · 2014: 39 · 2013: 43 · 2012: 30
- FWCI
- 4.49
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Cell Physiology (publishedVersion)
- PubMed (publishedVersion)
- Università Politecnica delle Marche (Università Politecnica delle Marche) (submittedVersion)
- 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 › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- white adipose tissue, CL316,243, beta3-adrenergic agonists, brown adipocyte differentiation, UCP1, UCP3, adipocyte origin, brown adipose tissue mitochondria, BrdU labeling
- MeSH terms
- Adipose Tissue, Adrenergic beta-Agonists, Animals, Adipose Tissue, Brown, Cell Line, Dioxoles, Immunohistochemistry, Male, Microscopy, Electron, Mitochondria, Rats, Sprague-Dawley, Adipocytes, Rats
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