Ablation of PPARγ in subcutaneous fat exacerbates age-associated obesity and metabolic decline
- PMID: 29383825
- PMCID: PMC5847881
- DOI: 10.1111/acel.12721
Ablation of PPARγ in subcutaneous fat exacerbates age-associated obesity and metabolic decline
Abstract
It is well established that aging is associated with metabolic dysfunction such as increased adiposity and impaired energy dissipation; however, the transcriptional mechanisms regulating energy balance during late life stages have not yet been fully elucidated. Here, we show that ablation of the nuclear receptor PPARγ specifically in inguinal fat tissue in aging mice is associated with increased fat tissue expansion and insulin resistance. These metabolic effects are accompanied by decreased thermogenesis, reduced levels of brown fat genes, and browning of subcutaneous adipose tissue. Comparative studies of the effects of PPARγ downregulation in young and mid-aged mice demonstrate a preferential regulation of brown fat gene programs in inguinal fat in an age-dependent manner. In conclusion, our study uncovers an essential role for PPARγ in maintaining energy expenditure during the aging process and suggests the possibility of targeting PPARγ to counteract age-associated metabolic dysfunction.
Keywords: PPARγ; aging; metabolic decline; obesity; subcutaneous fat.
© 2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
Figures
![Figure 1](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5847881/bin/ACEL-17-e12721-g001.gif)
![Figure 2](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5847881/bin/ACEL-17-e12721-g002.gif)
![Figure 3](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5847881/bin/ACEL-17-e12721-g003.gif)
![Figure 4](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5847881/bin/ACEL-17-e12721-g004.gif)
![Figure 5](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5847881/bin/ACEL-17-e12721-g005.gif)
![Figure 6](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5847881/bin/ACEL-17-e12721-g006.gif)
Similar articles
-
PexRAP Inhibits PRDM16-Mediated Thermogenic Gene Expression.Cell Rep. 2017 Sep 19;20(12):2766-2774. doi: 10.1016/j.celrep.2017.08.077. Cell Rep. 2017. PMID: 28930673 Free PMC article.
-
Beiging of white adipose tissue as a therapeutic strategy for weight loss in humans.Horm Mol Biol Clin Investig. 2017 Jun 23;31(2):/j/hmbci.2017.31.issue-2/hmbci-2017-0016/hmbci-2017-0016.xml. doi: 10.1515/hmbci-2017-0016. Horm Mol Biol Clin Investig. 2017. PMID: 28672737 Review.
-
Under the Surface of Subcutaneous Adipose Tissue Biology.Acta Dermatovenerol Croat. 2016 Dec;24(4):250-260. Acta Dermatovenerol Croat. 2016. PMID: 28128075 Review.
-
GQ-16, a TZD-Derived Partial PPARγ Agonist, Induces the Expression of Thermogenesis-Related Genes in Brown Fat and Visceral White Fat and Decreases Visceral Adiposity in Obese and Hyperglycemic Mice.PLoS One. 2016 May 3;11(5):e0154310. doi: 10.1371/journal.pone.0154310. eCollection 2016. PLoS One. 2016. PMID: 27138164 Free PMC article.
-
Inhibiting adipose tissue lipogenesis reprograms thermogenesis and PPARγ activation to decrease diet-induced obesity.Cell Metab. 2012 Aug 8;16(2):189-201. doi: 10.1016/j.cmet.2012.06.013. Cell Metab. 2012. PMID: 22863804 Free PMC article.
Cited by
-
Single-cell analysis reveals landscape of endometrial cancer response to estrogen and identification of early diagnostic markers.PLoS One. 2024 Mar 22;19(3):e0301128. doi: 10.1371/journal.pone.0301128. eCollection 2024. PLoS One. 2024. PMID: 38517922 Free PMC article.
-
Transcriptome-wide analysis reveals GYG2 as a mitochondria-related aging biomarker in human subcutaneous adipose tissue.Aging Cell. 2024 Feb;23(2):e14049. doi: 10.1111/acel.14049. Epub 2023 Dec 8. Aging Cell. 2024. PMID: 38062989 Free PMC article.
-
Effects of aging-induced obesity on the transcriptional expression of adipogenesis and thermogenic activity in the gonadal white adipose, brown adipose, and skeletal muscle tissues.Phys Act Nutr. 2023 Jun;27(2):39-49. doi: 10.20463/pan.2023.0017. Epub 2023 Jun 30. Phys Act Nutr. 2023. PMID: 37583071 Free PMC article.
-
Adipose Tissue Hyperplasia and Hypertrophy in Common and Syndromic Obesity-The Case of BBS Obesity.Nutrients. 2023 Aug 4;15(15):3445. doi: 10.3390/nu15153445. Nutrients. 2023. PMID: 37571382 Free PMC article. Review.
-
Lnc-TRTMFS promotes milk fat synthesis via the miR-132x/RAI14/mTOR pathway in BMECs.J Anim Sci. 2023 Jan 3;101:skad218. doi: 10.1093/jas/skad218. J Anim Sci. 2023. PMID: 37367933
References
-
- Gesta, S. , Tseng, Y. H. , & Kahn, C. R. (2007). Developmental origin of fat: tracking obesity to its source. Cell, 131, 242–256. - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases