Attainment of brown adipocyte features in white adipocytes of hormone-sensitive lipase null mice
Open accessAbstract
BACKGROUND: Hormone-sensitive lipase (HSL) is expressed predominantly in adipose tissue, where it plays an important role in catecholamine-stimulated hydrolysis of stored tri- and diglycerides, thus mobilizing fatty acids. HSL exhibits broad substrate specificity and besides acylglycerides it hydrolyzes cholesteryl esters, retinyl esters and lipoidal esters. Despite its role in fatty acid mobilization, HSL null mice have been shown to be resistant to diet-induced obesity. METHODOLOGY/PRINCIPAL FINDINGS: Following a high-fat diet (HFD) regimen, energy expenditure, measured using indirect calorimetry, was increased in HSL null mice. White adipose tissue of HSL null mice was characterized by reduced mass and reduced protein expression of PPARgamma, a key transcription factor in adipogenesis, and stearoyl-CoA desaturase 1, the expression of which is known to be positively correlated to the differentiation state of the adipocyte. The protein expression of uncoupling protein-1 (UCP-1), the highly specific marker of brown adipocytes, was increased 7-fold in white adipose tissue of HSL null mice compared to wildtype littermates. Transmission electron microscopy revealed an increase in the size of mitochondria of white adipocytes of HSL null mice. The mRNA expression of pRb and RIP140 was decreased in isolated white adipocytes, while the expression of UCP-1 and CPT1 was increased in HSL null mice compared to wildtype littermates. Basal oxygen consumption was increased almost 3-fold in white adipose tissue of HSL null mice and was accompanied by increased uncoupling activity. CONCLUSIONS: These data suggest that HSL is involved in the determination of white versus brown adipocytes during adipocyte differentiation The exact mechanism(s) underlying this novel role of HSL remains to be elucidated, but it seems clear that HSL is required to sustain normal expression levels of pRb and RIP140, which both promote differentiation into the white, rather than the brown, adipocyte lineage.
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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 [174]
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- Authors
- Ström, K., Hansson, O., Lucas, S., Nevsten, P., Fernandez, C., Klint, C., Movérare-Skrtic, S., Sundler, F., Ohlsson, C., & Holm, C.
- Affiliations
- Lund University (SE)
- University of Gothenburg (SE)
- Corresponding author
- Ström, Kristoffer
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2008-03-12
- Volume
- 3
- Issue
- 3
- Pages
- e1793
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC2258419
- OpenAlex
- W1992962137
- Cited by
- 62
- References
- 51
- Citations by year
- 2024: 1 · 2021: 2 · 2020: 1 · 2019: 3 · 2018: 1 · 2017: 3 · 2016: 3 · 2015: 5 · 2014: 2 · 2013: 8 · 2012: 7
- FWCI
- 5.87
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- Stiftelsen för Strategisk Forskning
- Knut och Alice Wallenbergs Stiftelse
- Novo Nordisk
- Vetenskapsrådet (11284)
- Topics
- Health Sciences › Medicine › Physiology › 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
- hormone-sensitive lipase, white adipocytes, brown adipocyte differentiation, UCP1, PPARγ, stearoyl-CoA desaturase 1, retinyl ester hydrolase, RIP140, retinoblastoma protein, high-fat diet, energy expenditure, mitochondrial uncoupling, adipogenesis
- MeSH terms
- Animals, Adipose Tissue, Brown, Cell Differentiation, Sterol Esterase, Diet, Female, Male, Mice, Inbred C57BL, Obesity, Adipocytes, Mice, Knockout, Microscopy, Electron, Transmission, Mice
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