Directing visceral white adipocyte precursors to a thermogenic adipocyte fate improves insulin sensitivity in obese mice
- University of Texas Southwestern Medical Center, United States
Abstract
Visceral adiposity confers significant risk for developing metabolic disease in obesity whereas preferential expansion of subcutaneous white adipose tissue (WAT) appears protective. Unlike subcutaneous WAT, visceral WAT is resistant to adopting a protective thermogenic phenotype characterized by the accumulation of Ucp1+ beige/BRITE adipocytes (termed "browning"). In this study, we investigated the physiological consequences of browning murine visceral WAT by selective genetic ablation of Zfp423, a transcriptional suppressor of the adipocyte thermogenic program. Zfp423 deletion in fetal visceral adipose precursors (Zfp423loxP/loxP; Wt1-Cre), or adult visceral white adipose precursors (PdgfrbrtTA; TRE-Cre; Zfp423loxP/loxP), results in the accumulation of beige-like thermogenic adipocytes within multiple visceral adipose depots. Thermogenic visceral WAT improves cold tolerance and prevents and reverses insulin resistance in obesity. These data indicate that beneficial visceral WAT browning can be engineered by directing visceral white adipocyte precursors to a thermogenic adipocyte fate, and suggest a novel strategy to combat insulin resistance in obesity.
Data availability
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Adipose tissue from β-3 agonist-treated micePublicly available at the NCBI Gene Expression Omnibus (accession no: GSE98132).
Article and author information
Author details
Funding
National Institutes of Health (R01 DK104789)
- Rana K Gupta
National Institutes of Health (R00-DK094973)
- William L Holland
American Heart Association (16POST26420136)
- Mengle Shao
Searle Scholars Program
- Rana K Gupta
Juvenile Diabetes Research Foundation (5-CDA-2014-185-A-N)
- William L Holland
National Institutes of Health (F30 DK100095)
- Jonathan Y Xia
National Institutes of Health (T32 GM008203)
- Chelsea Hepler
National Institutes of Health (F31DK113696)
- Chelsea Hepler
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (APN 2012-0072 and APN 2015-101207 ) of UTSW Medical Center.
Copyright
© 2017, Hepler et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Directing visceral white adipocyte precursors to a thermogenic adipocyte fate improves insulin sensitivity in obese mice
eLife 6:e27669.
https://doi.org/10.7554/eLife.27669
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