Chronic cold exposure induces autophagy to promote fatty acid oxidation, mitochondrial turnover, and thermogenesis in brown adipose tissue

Winifred W Yau; Kiraely Adam Wong; Jin Zhou; Nivetha Kanakaram Thimmukonda; Yajun Wu; Boon-Huat Bay; Brijesh Kumar Singh; Paul Michael Yen

doi:10.1016/j.isci.2021.102434

Chronic cold exposure induces autophagy to promote fatty acid oxidation, mitochondrial turnover, and thermogenesis in brown adipose tissue

iScience. 2021 Apr 15;24(5):102434. doi: 10.1016/j.isci.2021.102434. eCollection 2021 May 21.

Authors

Winifred W Yau¹, Kiraely Adam Wong¹, Jin Zhou¹, Nivetha Kanakaram Thimmukonda¹, Yajun Wu², Boon-Huat Bay², Brijesh Kumar Singh¹, Paul Michael Yen^{1

3}

Affiliations

¹ Laboratory of Hormonal Regulation, Cardiovascular and Metabolic Disorders Program, Duke NUS Medical School, Singapore 169857, Singapore.
² Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117594, Singapore.
³ Duke Molecular Physiology Institute, Duke University, Durham, NC 27708, USA.

Abstract

Autophagy plays an important role in lipid breakdown, mitochondrial turnover, and mitochondrial function during brown adipose tissue (BAT) activation by thyroid hormone, but its role in BAT during adaptive thermogenesis remains controversial. Here, we examined BAT from mice exposed to 72 h of cold challenge as well as primary brown adipocytes treated with norepinephrine and found increased autophagy as well as increased β-oxidation, mitophagy, mitochondrial turnover, and mitochondrial activity. To further understand the role of autophagy of BAT in vivo, we generated BAT-specific Atg5 knockout (Atg5cKO) mice and exposed them to cold for 72 h. Interestingly, BAT-specific Atg5cKO mice were unable to maintain body temperature after chronic cold exposure and displayed deranged mitochondrial morphology and reactive oxygen species damage in their BAT. Our findings demonstrate the critical role of autophagy in adaptive thermogenesis, fatty acid metabolism, and mitochondrial function in BAT during chronic cold exposure.

Keywords: Cell Biology; Endocrine System Physiology; Molecular Physiology.