Arsenite exposure suppresses adipogenesis, mitochondrial biogenesis and thermogenesis via autophagy inhibition in brown adipose tissue

Authors

Jiyoung Bae, University of Nebraska- Lincoln & University of Wisconsin School of Medicine and Public Health
Yura Jang, University of Nebraska- Lincoln & The Johns Hopkins University School of Medicine
Heejeong Kim, University of Nebraska- Lincoln
Kalika Mahato, University of Nebraska- Lincoln
cameron Schaecher, University of Nebraska- Lincoln & University of Nebraska Medical Center, Omaha,
Issac M. Kim, University of Nebraska- Lincoln
Eunju Kim, University of Nebraska- Lincoln
Seung-Hyun Ro, University of Nebraska-LincolnFollow

ORCID IDs

http://orcid.org/0000-0002-7744-7615

Document Type

Article

Date of this Version

2019

Citation

Scientific RepoRtS (2019) 9:14464 | https://doi.org/10.1038/s41598-019-50965-9 1

Comments

The Author(s) 2019

Abstract

Arsenite, a trivalent form of arsenic, is an element that occurs naturally in the environment. Humans are exposed to high dose of arsenite through consuming arsenite-contaminated drinking water and food, and the arsenite can accumulate in the human tissues. Arsenite induces oxidative stress, which is linked to metabolic disorders such as obesity and diabetes. Brown adipocytes dissipating energy as heat have emerging roles for obesity treatment and prevention. therefore, understanding the pathophysiological role of brown adipocytes can provide effective strategies delineating the link between arsenite exposure and metabolic disorders. Our study revealed that arsenite significantly reduced differentiation of murine brown adipocytes and mitochondrial biogenesis and respiration, leading to attenuated thermogenesis via decreasing UCP1 expression. Oral administration of arsenite in mice resulted in heavy accumulation in brown adipose tissue and suppression of lipogenesis, mitochondrial biogenesis and thermogenesis.Mechanistically, arsenite exposure significantly inhibited autophagy necessary for homeostasis of brown adipose tissue through suppression of Sestrin2 and ULK1. These results clearly confirm the emerging mechanisms underlying the implications of arsenite exposure in metabolic disorders.