Journal
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
Volume 312, Issue 1, Pages R74-R84Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpregu.00425.2016
Keywords
obesity; inflammation; insulin resistance; glucose intolerance
Categories
Funding
- Cardiometabolic Disease Research Foundation
- Sears Trust Research Foundation
- National Institutes of Health (NIH) [K01 HL-125503, R21 DK-105368]
- MU Research Council
- MU Richard Wallace Faculty Incentive Grant
- NIH Initiative for Maximizing Student Diversity EXPRESS Fellows Program [R25GM056901]
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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 degrees 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 similar to 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.
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