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J Biol Chem. 2017 Oct 6;292(40):16616-16625. doi: 10.1074/jbc.M117.790451. Epub 2017 Aug 9.

Both brown adipose tissue and skeletal muscle thermogenesis processes are activated during mild to severe cold adaptation in mice.

Author information

1
From the School of Biotechnology, KIIT University, Bhubaneswar, Odisha 751024, India, naresh.bal@kiitbiotech.ac.in.
2
the Department of Physiology and Cell Biology, College of Medicine, Ohio State University, Columbus, Ohio 43210, and.
3
the Sanford Burnham Prebys Medical Discovery Institute at Lake Nona, Orlando, Florida 32827.
4
From the School of Biotechnology, KIIT University, Bhubaneswar, Odisha 751024, India.
5
the Department of Physiology and Cell Biology, College of Medicine, Ohio State University, Columbus, Ohio 43210, and mperiasamy@sbpdiscovery.org.

Abstract

Thermogenesis is an important homeostatic mechanism essential for survival and normal physiological functions in mammals. Both brown adipose tissue (BAT) (i.e. uncoupling protein 1 (UCP1)-based) and skeletal muscle (i.e. sarcolipin (SLN)-based) thermogenesis processes play important roles in temperature homeostasis, but their relative contributions differ from small to large mammals. In this study, we investigated the functional interplay between skeletal muscle- and BAT-based thermogenesis under mild versus severe cold adaptation by employing UCP1-/- and SLN-/- mice. Interestingly, adaptation of SLN-/- mice to mild cold conditions (16 °C) significantly increased UCP1 expression, suggesting increased reliance on BAT-based thermogenesis. This was also evident from structural alterations in BAT morphology, including mitochondrial architecture, increased expression of electron transport chain proteins, and depletion of fat droplets. Similarly, UCP1-/- mice adapted to mild cold up-regulated muscle-based thermogenesis, indicated by increases in muscle succinate dehydrogenase activity, SLN expression, mitochondrial content, and neovascularization, compared with WT mice. These results further confirm that SLN-based thermogenesis is a key player in muscle non-shivering thermogenesis (NST) and can compensate for loss of BAT activity. We also present evidence that the increased reliance on BAT-based NST depends on increased autonomic input, as indicated by abundant levels of tyrosine hydroxylase and neuropeptide Y. Our findings demonstrate that both BAT and muscle-based NST are equally recruited during mild and severe cold adaptation and that loss of heat production from one thermogenic pathway leads to increased recruitment of the other, indicating a functional interplay between these two thermogenic processes.

KEYWORDS:

adipose tissue; calcium ATPase; calcium-binding protein; skeletal muscle; uncoupling protein

PMID:
28794154
PMCID:
PMC5633124
DOI:
10.1074/jbc.M117.790451
[Indexed for MEDLINE]
Free PMC Article

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