title: Loss of UCP1 exacerbates Western diet-induced glycemic dysregulation independent of changes in body weight in female mice.
abstract: We tested the hypothesis that female mice null for uncoupling protein 1 (UCP1) would have increased susceptibility to Western diet-induced "whitening" of brown adipose tissue (AT) and glucose intolerance. Six-week-old C57BL/6J wild-type (WT) and UCP1 knockout (UCP1-/-) mice, housed at 25°C, were randomized to either a control diet (10% kcal from fat) or Western diet (45% kcal from fat and 1% cholesterol) for 28 wk. Loss of UCP1 had no effect on energy intake, energy expenditure, spontaneous physical activity, weight gain, or visceral white AT mass. Despite similar susceptibility to weight gain compared with WT, UCP1-/-exhibited whitening of brown AT evidenced by a striking ~500% increase in mass and appearance of large unilocular adipocytes, increased expression of genes related to inflammation, immune cell infiltration, and endoplasmic reticulum/oxidative stress (P < 0.05), and decreased mitochondrial subunit protein (COX I, II, III, and IV, P < 0.05), all of which were exacerbated by Western diet (P < 0.05). UCP1-/-mice also developed liver steatosis and glucose intolerance, which was worsened by Western diet. Collectively, these findings demonstrate that loss of UCP1 exacerbates Western diet-induced whitening of brown AT, glucose intolerance, and induces liver steatosis. Notably, the adverse metabolic manifestations of UCP1-/-were independent of changes in body weight, visceral adiposity, and energy expenditure. These novel findings uncover a previously unrecognized metabolic protective role of UCP1 that is independent of its already established role in energy homeostasis.
authors.affiliation: Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri.
authors.forename: Nathan C
authors.initials: NC
authors.lastname: Winn
authors.affiliation: Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri.
authors.forename: Victoria J
authors.identifier: 0000-0001-7563-0806
authors.initials: VJ
authors.lastname: Vieira-Potter
authors.affiliation: Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri.
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Gastecki
authors.affiliation: Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Welly
authors.affiliation: Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Scroggins
authors.affiliation: Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri.
authors.forename: Terese M
authors.initials: TM
authors.lastname: Zidon
authors.affiliation: Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri.
authors.forename: T'Keaya L
authors.initials: TL
authors.lastname: Gaines
authors.affiliation: Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri.
authors.forename: Makenzie L
authors.initials: ML
authors.lastname: Woodford
authors.affiliation: Transgenic Animal Core, University of Missouri, Columbia, Missouri.
authors.forename: Natalia G
authors.initials: NG
authors.lastname: Karasseva
authors.affiliation: Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri.
authors.forename: Jill A
authors.initials: JA
authors.lastname: Kanaley
authors.affiliation: Endocrine and Diabetes Division, Veterans Greater Los Angeles Healthcare System and Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California.
authors.forename: Harold S
authors.initials: HS
authors.lastname: Sacks
authors.affiliation: Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri; padillaja@missouri.edu.|Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri; and.|Child Health, University of Missouri, Columbia, Missouri.
authors.forename: Jaume
authors.initials: J
authors.lastname: Padilla
mesh_terms: D002001:Adipose Tissue, Brown / Q000503:physiopathology; D000818:Animals; D001835:Body Weight; D066273:Diet, Western / Q000009:adverse effects*; D005234:Fatty Liver / Q000209:etiology* / Q000503:physiopathology*; D005260:Female; D018149:Glucose Intolerance / Q000209:etiology* / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000209:etiology / Q000503:physiopathology; D000071256:Uncoupling Protein 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: C000604371:UCP1 protein, human; D000071256:Uncoupling Protein 1
keywords: glucose intolerance; inflammation; insulin resistance; obesity