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Up-Regulation of Mitochondrial Activity and Acquirement of Brown Adipose Tissue-Like Property in the White Adipose Tissue of Fsp27 Deficient Mice
Open accessAbstract
Fsp27, a member of the Cide family proteins, was shown to localize to lipid droplet and promote lipid storage in adipocytes. We aimed to understand the biological role of Fsp27 in regulating adipose tissue differentiation, insulin sensitivity and energy balance. Fsp27(-/-) mice and Fsp27/lep double deficient mice were generated and we examined the adiposity, whole body metabolism, BAT and WAT morphology, insulin sensitivity, mitochondrial activity, and gene expression changes in these mouse strains. Furthermore, we isolated mouse embryonic fibroblasts (MEFs) from wildtype and Fsp27(-/-) mice, followed by their differentiation into adipocytes in vitro. We found that Fsp27 is expressed in both brown adipose tissue (BAT) and white adipose tissue (WAT) and its levels were significantly elevated in the WAT and liver of leptin-deficient ob/ob mice. Fsp27(-/-) mice had increased energy expenditure, lower levels of plasma triglycerides and free fatty acids. Furthermore, Fsp27(-/-)and Fsp27/lep double-deficient mice are resistant to diet-induced obesity and display increased insulin sensitivity. Moreover, white adipocytes in Fsp27(-/-) mice have reduced triglycerides accumulation and smaller lipid droplets, while levels of mitochondrial proteins, mitochondrial size and activity are dramatically increased. We further demonstrated that BAT-specific genes and key metabolic controlling factors such as FoxC2, PPAR and PGC1alpha were all markedly upregulated. In contrast, factors inhibiting BAT differentiation such as Rb, p107 and RIP140 were down-regulated in the WAT of Fsp27(-/-) mice. Remarkably, Fsp27(-/-) MEFs differentiated in vitro show many brown adipocyte characteristics in the presence of the thyroid hormone triiodothyronine (T3). Our data thus suggest that Fsp27 acts as a novel regulator in vivo to control WAT identity, mitochondrial activity and insulin sensitivity.
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“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 [176]
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“For example, Toh et al. (176) and Nishino,et al. (205) find that mice deficient in Fsp27, a lipid droplet protein that promotes lipid storage in white and brown adipocytes, have increased whole-body energy expenditure, resistance to diet-induced obesity, and enhanced insulin sensitivity.”
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Metadata
- Authors
- Toh, S. Y., Gong, J., Du, G., Li, J. Z., Yang, S., Ye, J., Yao, H., Zhang, Y., Xue, B., Li, Q., Yang, H., Wen, Z., & Li, P.
- Affiliations
- Hong Kong University of Science and Technology (HK)
- Tsinghua University (CN)
- Air Force Medical University (CN)
- UNSW Sydney (AU)
- Corresponding author
- Li, Peng
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2008-08-06
- Volume
- 3
- Issue
- 8
- Pages
- e2890
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC2483355
- OpenAlex
- W1998949529
- Cited by
- 267
- References
- 47
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 10 · 2023: 7 · 2022: 10 · 2021: 7 · 2020: 8 · 2019: 11 · 2018: 11 · 2017: 17 · 2016: 11 · 2015: 21 · 2014: 24 · 2013: 28 · 2012: 25
- FWCI
- 13.81
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- National University of Singapore
- National Natural Science Foundation of China (30530350)
- Ministry of Education of the People's Republic of China (704002)
- Tsinghua University
- Xiamen University
- Changjiang Scholar Program of Chinese Ministry of Education
- National Key Research and Development Program of China (2007CB914404, 2006CB503900)
- Program for Changjiang Scholars and Innovative Research Team in University
- Topics
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- FSP27, white adipose tissue, brown adipose tissue, mitochondrial activity, insulin sensitivity, energy balance, diet-induced obesity, leptin, lipid droplets, adipogenesis, FOXC2, PGC-1α, peroxisome proliferator-activated receptors, RIP140, triiodothyronine, ob/ob mice
- MeSH terms
- Adipose Tissue, Animals, Adipose Tissue, Brown, Gene Expression Regulation, Insulin, Mice, Obese, Mitochondria, Phenotype, Proteins, Thinness, Mice, Knockout, Leptin, Gene Expression Profiling, Mice
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