Publication Date

1-1-2021

Journal

Frontiers in Aging

DOI

10.3389/fragi.2021.803482

PMID

35822007

PMCID

PMC9261351

PubMedCentral® Posted Date

2-2-2022

PubMedCentral® Full Text Version

Post-Print

Published Open-Access

yes

Keywords

Spi1/PU.1, thermogenesis, energy expenditure, inflammation, insulin resistance, obesity, aging, adipocyte

Abstract

Objective: Although PU.1/Spi1 is known as a master regulator for macrophage development and function, we have reported previously that it is also expressed in adipocytes and is transcriptionally induced in obesity. Here, we investigated the role of adipocyte PU.1 in the development of the age-associated metabolic syndrome.

Methods: We generated mice with adipocyte-specific PU.1 knockout, assessed metabolic changes in young and older adult PU.1fl/fl (control) and AdipoqCre PU.1fl/fl (aPU.1KO) mice, including body weight, body composition, energy expenditure, and glucose homeostasis. We also performed transcriptional analyses using RNA-Sequencing of adipocytes from these mice.

Results: aPU.1KO mice have elevated energy expenditure at a young age and decreased adiposity and increased insulin sensitivity in later life. Corroborating these observations, transcriptional network analysis indicated the existence of validated, adipocyte PU.1-modulated regulatory hubs that direct inflammatory and thermogenic gene expression programs.

Conclusion: Our data provide evidence for a previously uncharacterized role of PU.1 in the development of age-associated obesity and insulin resistance.

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