miR-155 Deletion in Female Mice Prevents Diet-Induced Obesity

Obesity is a growing epidemic in developed countries. Obese individuals are susceptible to comorbidities, including cardiovascular disease and metabolic disorder. Increasing the ability of adipose tissue to expend excess energy could improve protection from obesity. One promising target is microRNA...

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Main Authors:	Gaudet, Andrew D., Fonken, Laura K., Gushchina, Liubov V., Aubrecht, Taryn G., Maurya, Santosh K., Periasamy, Muthu, Nelson, Randy J., Popovich, Phillip G.
Format:	Online
Language:	English
Published:	Nature Publishing Group 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4782173/

id	pubmed-4782173
recordtype	oai_dc
spelling	pubmed-47821732016-03-10 miR-155 Deletion in Female Mice Prevents Diet-Induced Obesity Gaudet, Andrew D. Fonken, Laura K. Gushchina, Liubov V. Aubrecht, Taryn G. Maurya, Santosh K. Periasamy, Muthu Nelson, Randy J. Popovich, Phillip G. Article Obesity is a growing epidemic in developed countries. Obese individuals are susceptible to comorbidities, including cardiovascular disease and metabolic disorder. Increasing the ability of adipose tissue to expend excess energy could improve protection from obesity. One promising target is microRNA (miR)-155-5p. We demonstrate that deletion of miR-155 (-5p and -3p) in female mice prevents diet-induced obesity. Body weight gain did not differ between wild-type (WT) and miR-155 knockout (KO) mice fed control diet (CD); however, miR-155 KO mice fed high-fat diet (HFD) gained 56% less body weight and 74% less gonadal white adipose tissue (WAT) than WT mice. Enhanced WAT thermogenic potential, brown adipose tissue differentiation, and/or insulin sensitivity might underlie this obesity resistance. Indeed, miR-155 KO mice on HFD had 21% higher heat release than WT HFD mice. Compared to WT adipocytes, miR-155 KO adipocytes upregulated brown (Ucp1, Cidea, Pparg) and white (Fabp4, Pnpla2, AdipoQ, Fasn) adipogenic genes, and glucose metabolism genes (Glut4, Irs1). miR-155 deletion abrogated HFD-induced adipocyte hypertrophy and WAT inflammation. Therefore, miR-155 deletion increases adipogenic, insulin sensitivity, and energy uncoupling machinery, while limiting inflammation in WAT, which together could restrict HFD-induced fat accumulation. Our results identify miR-155 as a novel candidate target for improving obesity resistance. Nature Publishing Group 2016-03-08 /pmc/articles/PMC4782173/ /pubmed/26953132 http://dx.doi.org/10.1038/srep22862 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Gaudet, Andrew D. Fonken, Laura K. Gushchina, Liubov V. Aubrecht, Taryn G. Maurya, Santosh K. Periasamy, Muthu Nelson, Randy J. Popovich, Phillip G.
spellingShingle	Gaudet, Andrew D. Fonken, Laura K. Gushchina, Liubov V. Aubrecht, Taryn G. Maurya, Santosh K. Periasamy, Muthu Nelson, Randy J. Popovich, Phillip G. miR-155 Deletion in Female Mice Prevents Diet-Induced Obesity
author_facet	Gaudet, Andrew D. Fonken, Laura K. Gushchina, Liubov V. Aubrecht, Taryn G. Maurya, Santosh K. Periasamy, Muthu Nelson, Randy J. Popovich, Phillip G.
author_sort	Gaudet, Andrew D.
title	miR-155 Deletion in Female Mice Prevents Diet-Induced Obesity
title_short	miR-155 Deletion in Female Mice Prevents Diet-Induced Obesity
title_full	miR-155 Deletion in Female Mice Prevents Diet-Induced Obesity
title_fullStr	miR-155 Deletion in Female Mice Prevents Diet-Induced Obesity
title_full_unstemmed	miR-155 Deletion in Female Mice Prevents Diet-Induced Obesity
title_sort	mir-155 deletion in female mice prevents diet-induced obesity
description	Obesity is a growing epidemic in developed countries. Obese individuals are susceptible to comorbidities, including cardiovascular disease and metabolic disorder. Increasing the ability of adipose tissue to expend excess energy could improve protection from obesity. One promising target is microRNA (miR)-155-5p. We demonstrate that deletion of miR-155 (-5p and -3p) in female mice prevents diet-induced obesity. Body weight gain did not differ between wild-type (WT) and miR-155 knockout (KO) mice fed control diet (CD); however, miR-155 KO mice fed high-fat diet (HFD) gained 56% less body weight and 74% less gonadal white adipose tissue (WAT) than WT mice. Enhanced WAT thermogenic potential, brown adipose tissue differentiation, and/or insulin sensitivity might underlie this obesity resistance. Indeed, miR-155 KO mice on HFD had 21% higher heat release than WT HFD mice. Compared to WT adipocytes, miR-155 KO adipocytes upregulated brown (Ucp1, Cidea, Pparg) and white (Fabp4, Pnpla2, AdipoQ, Fasn) adipogenic genes, and glucose metabolism genes (Glut4, Irs1). miR-155 deletion abrogated HFD-induced adipocyte hypertrophy and WAT inflammation. Therefore, miR-155 deletion increases adipogenic, insulin sensitivity, and energy uncoupling machinery, while limiting inflammation in WAT, which together could restrict HFD-induced fat accumulation. Our results identify miR-155 as a novel candidate target for improving obesity resistance.
publisher	Nature Publishing Group
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4782173/
_version_	1613548622079590400

miR-155 Deletion in Female Mice Prevents Diet-Induced Obesity

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