Dataset Information

ESRRG and PERM1 Govern Mitochondrial Conversion in Brite/Beige Adipocyte Formation.

ABSTRACT: When exposed to cold temperatures, mice increase their thermogenic capacity by an expansion of brown adipose tissue mass and the formation of brite/beige adipocytes in white adipose tissue depots. However, the process of the transcriptional changes underlying the conversion of a phenotypic white to brite/beige adipocytes is only poorly understood. By analyzing transcriptome profiles of inguinal adipocytes during cold exposure and in mouse models with a different propensity to form brite/beige adipocytes, we identified ESRRG and PERM1 as modulators of this process. The production of heat by mitochondrial uncoupled respiration is a key feature of brite/beige compared to white adipocytes and we show here that both candidates are involved in PGC1? transcriptional network to positively regulate mitochondrial capacity. Moreover, we show that an increased expression of ESRRG or PERM1 supports the formation of brown or brite/beige adipocytes in vitro and in vivo. These results reveal that ESRRG and PERM1 are early induced in and important regulators of brite/beige adipocyte formation.

SUBMITTER: Muller S

PROVIDER: S-EPMC7304443 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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ESRRG and PERM1 Govern Mitochondrial Conversion in Brite/Beige Adipocyte Formation.

Müller Sebastian S Perdikari Aliki A Dapito Dianne H DH Sun Wenfei W Wollscheid Bernd B Balaz Miroslav M Wolfrum Christian C

Frontiers in endocrinology 20200612

When exposed to cold temperatures, mice increase their thermogenic capacity by an expansion of brown adipose tissue mass and the formation of brite/beige adipocytes in white adipose tissue depots. However, the process of the transcriptional changes underlying the conversion of a phenotypic white to brite/beige adipocytes is only poorly understood. By analyzing transcriptome profiles of inguinal adipocytes during cold exposure and in mouse models with a different propensity to form brite/beige ad ...[more]

PMID: 32595605

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Project description:Highly active antiretroviral therapy has remarkably improved quality of life of HIV-1-infected patients. However, this treatment has been associated with the so-called lipodystrophic syndrome, which conveys a number of adverse metabolic effects and morphological alterations. Among them, lipoatrophy of subcutaneous fat in certain anatomical areas and hypertrophy of visceral depots are the most common. Less frequently, lipomatous enlargements of subcutaneous fat at distinct anatomic areas occur. Lipomatous adipose tissue in the dorso-cervical area ("buffalo hump") has been associated with a partial white-to-brown phenotype transition and with increased cell proliferation, but, to date, lipomatous enlargements arising in other parts of the body have not been characterized. In order to establish the main molecular events associated with the appearance of lipomatosis in HIV-1 patients, we analyzed biopsies of lipomatous tissue from "buffalo hump" and from other anatomical areas in patients, in comparison with healthy subcutaneous adipose tissue, using a marker gene expression approach. Both buffalo-hump and non-buffalo-hump lipomatous adipose tissues exhibited similar patterns of non-compromised adipogenesis, unaltered inflammation, non-fibrotic phenotype and proliferative activity. Shorter telomere length, prelamin A accumulation and SA-β-Gal induction, reminiscent of adipocyte senescence, were also common to both types of lipomatous tissues. Buffalo hump biopsies showed expression of marker genes of brown adipose tissue (e.g. UCP1) and, specifically, of "classical" brown adipocytes (e.g. ZIC1) but not of beige/brite adipocytes. No such brown fat-related gene expression occurred in lipomatous tissues at other anatomical sites. In conclusion, buffalo hump and other subcutaneous adipose tissue enlargements from HIV-1-infected patients share a similar lipomatous character. However, a distorted induction of white-to-"classical brown adipocyte" phenotype appears unique of dorso-cervical lipomatosis. Thus, the insults caused by HIV-1 viral infection and/or antiretroviral therapy leading to lipomatosis are acting in a location- and adipocyte lineage-dependent manner.

Dataset Information

ESRRG and PERM1 Govern Mitochondrial Conversion in Brite/Beige Adipocyte Formation.

Publications

ESRRG and PERM1 Govern Mitochondrial Conversion in Brite/Beige Adipocyte Formation.

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