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Brown adipose tissue metabolism in arsenic environmental health and obesity
Author(s) -
Ro SeungHyun,
Jang Yura,
Bae Jiyoung
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.lb271
Subject(s) - thermogenesis , brown adipose tissue , arsenic , thermogenin , endocrinology , medicine , adipose tissue , mitochondrial biogenesis , biology , mitochondrion , chemistry , microbiology and biotechnology , organic chemistry
Arsenic is an element that occurs naturally in the environment. Humans are likely to be exposed to higher amount of arsenic through arsenic contaminated drinking water and consuming foods including fruits and vegetables, and the arsenic can accumulate in the human body at high concentrations. Previous research has shown that arsenic induces oxidative stress linked to metabolic diseases such as obesity and diabetes. In mice, arsenic exposure during embryonic development is linked to an early puberty and adult obesity. Recent findings of brown adipocytes, capable of dissipating energy as heat, in adult humans have promised new hope for obesity treatment and prevention. Therefore, understanding the pathophysiological role of brown adipocytes and uncoupling protein 1 (UCP1) regulation in thermogenesis can provide effective strategies against obesity. Here, we investigated the effects of arsenic on differentiation, mitochondrial respiration and thermogenesis in immortalized murine brown adipocytes. We observed that arsenic significantly reduced brown adipocyte differentiation in dose dependent manner. Arsenic suppressed mitochondrial respiration and biogenesis, leading to attenuated brown adipocytes specific thermogenesis functions including UCP1 in immortalized murine brown adipocytes. In mice studies, we confirmed the heavy arsenic accumulation in brown adipose tissue (BAT) and the suppression of gene expression levels of mitochondria specific markers after the oral administration of arsenic into mice at dose of 10 mg/kg/day for 9 days. Arsenic significantly suppressed the BAT thermogenesis marker UCP1 when exposed to cold temperature for 24 hr at the last day of oral gavage. These results reveal the underlying mechanism of how arsenic aggravates metabolic diseases such as obesity by suppressing brown adipocyte differentiation, mitochondria function and thermogenesis, which can be utilized for development of arsenic‐specific inhibitor drugs protecting essential physiological functions of BAT in humans. Support or Funding Information This work was supported by University of Nebraska‐Lincoln ARD/ORED/BIOC grants, Layman award, Nebraska Tobacco Settlement‐Biomedical research enhancement funds, and Nebraska Center for thePrevention of Obesity Diseases (NPOD) seed grant from NIH (P20GM104320) to S.R. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .