title: miR-155 Deletion in Female Mice Prevents Diet-Induced Obesity.
abstract: 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.
authors.affiliation: Department of Neuroscience, Wexner Medical Center, The Ohio State University, Biomedical Research Tower 6th floor 460 W. 12th Ave Columbus, OH 43210 USA.|Center for Brain and Spinal Cord Repair, Wexner Medical Center, The Ohio State University, Biomedical Research Tower 6th floor 460 W. 12th Ave Columbus, OH 43210 USA.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Gaudet
authors.affiliation: Department of Neuroscience, Wexner Medical Center, The Ohio State University, Biomedical Research Tower 6th floor 460 W. 12th Ave Columbus, OH 43210 USA.|Institute for Behavioral Medicine Research, Wexner Medical Center, The Ohio State University, Biomedical Research Tower 6th floor 460 W. 12th Ave Columbus, OH 43210 USA.
authors.forename: Laura K
authors.initials: LK
authors.lastname: Fonken
authors.affiliation: Department of Physiology and Cell Biology, Wexner Medical Center, The Ohio State University, Biomedical Research Tower 6th floor, 460 W. 12th Ave, Columbus, OH 43210 USA.
authors.forename: Liubov V
authors.initials: LV
authors.lastname: Gushchina
authors.affiliation: Department of Neuroscience, Wexner Medical Center, The Ohio State University, Biomedical Research Tower 6th floor 460 W. 12th Ave Columbus, OH 43210 USA.|Institute for Behavioral Medicine Research, Wexner Medical Center, The Ohio State University, Biomedical Research Tower 6th floor 460 W. 12th Ave Columbus, OH 43210 USA.
authors.forename: Taryn G
authors.initials: TG
authors.lastname: Aubrecht
authors.affiliation: Department of Physiology and Cell Biology, Wexner Medical Center, The Ohio State University, Biomedical Research Tower 6th floor, 460 W. 12th Ave, Columbus, OH 43210 USA.
authors.forename: Santosh K
authors.initials: SK
authors.lastname: Maurya
authors.affiliation: Department of Physiology and Cell Biology, Wexner Medical Center, The Ohio State University, Biomedical Research Tower 6th floor, 460 W. 12th Ave, Columbus, OH 43210 USA.
authors.forename: Muthu
authors.initials: M
authors.lastname: Periasamy
authors.affiliation: Department of Neuroscience, Wexner Medical Center, The Ohio State University, Biomedical Research Tower 6th floor 460 W. 12th Ave Columbus, OH 43210 USA.|Institute for Behavioral Medicine Research, Wexner Medical Center, The Ohio State University, Biomedical Research Tower 6th floor 460 W. 12th Ave Columbus, OH 43210 USA.
authors.forename: Randy J
authors.initials: RJ
authors.lastname: Nelson
authors.affiliation: Department of Neuroscience, Wexner Medical Center, The Ohio State University, Biomedical Research Tower 6th floor 460 W. 12th Ave Columbus, OH 43210 USA.|Center for Brain and Spinal Cord Repair, Wexner Medical Center, The Ohio State University, Biomedical Research Tower 6th floor 460 W. 12th Ave Columbus, OH 43210 USA.|Institute for Behavioral Medicine Research, Wexner Medical Center, The Ohio State University, Biomedical Research Tower 6th floor 460 W. 12th Ave Columbus, OH 43210 USA.
authors.forename: Phillip G
authors.initials: PG
authors.lastname: Popovich
mesh_terms: D050156:Adipogenesis / Q000235:genetics*; D002001:Adipose Tissue, Brown / Q000378:metabolism; D052436:Adipose Tissue, White / Q000378:metabolism*; D050154:Adiposity / Q000235:genetics*; D000818:Animals; D001835:Body Weight / Q000235:genetics; D016026:Bone Marrow Transplantation; D059305:Diet, High-Fat; D005260:Female; D017353:Gene Deletion; D005947:Glucose / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics*; D009765:Obesity / Q000235:genetics* / Q000517:prevention & control; D015430:Weight Gain / Q000235:genetics*
chemical_list: D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; D005947:Glucose