Directing visceral white adipocyte precursors to a thermogenic adipocyte fate improves insulin sensitivity in obese mice

Chelsea Hepler; Mengle Shao; Jonathan Y. Xia; Alexandra L. Ghaben; Mackenzie J. Pearson; Lavanya Vishvanath; Ankit X. Sharma; Thomas S. Morley; William L Holland; Rana K Gupta

doi:10.7554/eLife.27669

Directing visceral white adipocyte precursors to a thermogenic adipocyte fate improves insulin sensitivity in obese mice

Chelsea Hepler, Mengle Shao, Jonathan Y. Xia, Alexandra L. Ghaben, Mackenzie J. Pearson, Lavanya Vishvanath, Ankit X. Sharma, Thomas S. Morley, William L Holland, Rana K Gupta

Research output: Contribution to journal › Article › peer-review

33 Scopus citations

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 (Zfp423^loxP/loxP; Wt1-Cre), or adult visceral white adipose precursors (Pdgfrb^rtTA; TRE-Cre; Zfp423^loxP/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.

Original language	English (US)
Article number	e27669
Journal	eLife
Volume	6
DOIs	https://doi.org/10.7554/eLife.27669
State	Published - Jul 19 2017

ASJC Scopus subject areas

General Immunology and Microbiology
General Biochemistry, Genetics and Molecular Biology
General Neuroscience

Access to Document

10.7554/eLife.27669

Cite this

@article{60967c6654bd4b1ebe9cb2a7f8e7fae8,

title = "Directing visceral white adipocyte precursors to a thermogenic adipocyte fate improves insulin sensitivity in obese mice",

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 {\textquoteleft}browning{\textquoteright}). 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.",

author = "Chelsea Hepler and Mengle Shao and Xia, {Jonathan Y.} and Ghaben, {Alexandra L.} and Pearson, {Mackenzie J.} and Lavanya Vishvanath and Sharma, {Ankit X.} and Morley, {Thomas S.} and Holland, {William L} and Gupta, {Rana K}",

note = "Publisher Copyright: {\textcopyright} Hepler et al.",

year = "2017",

month = jul,

day = "19",

doi = "10.7554/eLife.27669",

language = "English (US)",

volume = "6",

journal = "eLife",

issn = "2050-084X",

publisher = "eLife Sciences Publications",

}

TY - JOUR

T1 - Directing visceral white adipocyte precursors to a thermogenic adipocyte fate improves insulin sensitivity in obese mice

AU - Hepler, Chelsea

AU - Shao, Mengle

AU - Xia, Jonathan Y.

AU - Ghaben, Alexandra L.

AU - Pearson, Mackenzie J.

AU - Vishvanath, Lavanya

AU - Sharma, Ankit X.

AU - Morley, Thomas S.

AU - Holland, William L

AU - Gupta, Rana K

PY - 2017/7/19

Y1 - 2017/7/19

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85029228053&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85029228053&partnerID=8YFLogxK

U2 - 10.7554/eLife.27669

DO - 10.7554/eLife.27669

M3 - Article

C2 - 28722653

AN - SCOPUS:85029228053

SN - 2050-084X

VL - 6

JO - eLife

JF - eLife

M1 - e27669

ER -

Directing visceral white adipocyte precursors to a thermogenic adipocyte fate improves insulin sensitivity in obese mice

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this