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Am J Physiol Regul Integr Comp Physiol. 2017 Jan 1;312(1):R74-R84. doi: 10.1152/ajpregu.00425.2016. Epub 2016 Nov 23.

Loss of UCP1 exacerbates Western diet-induced glycemic dysregulation independent of changes in body weight in female mice.

Author information

1
Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri.
2
Transgenic Animal Core, University of Missouri, Columbia, Missouri.
3
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.
4
Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri; padillaja@missouri.edu.
5
Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri; and.
6
Child Health, University of Missouri, Columbia, Missouri.

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.

KEYWORDS:

glucose intolerance; inflammation; insulin resistance; obesity

PMID:
27881400
PMCID:
PMC5283932
DOI:
10.1152/ajpregu.00425.2016
[Indexed for MEDLINE]
Free PMC Article

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