TFAM expression in brown adipocytes confers obesity resistance by secreting extracellular vesicles that promote self-activation

Masakazu Fujii; Daiki Setoyama; Kazuhito Gotoh; Yushi Dozono; Mikako Yagi; Masataka Ikeda; Tomomi Ide; Takeshi Uchiumi; Dongchon Kang

doi:10.1016/j.isci.2022.104889

TFAM expression in brown adipocytes confers obesity resistance by secreting extracellular vesicles that promote self-activation

iScience. 2022 Aug 10;25(9):104889. doi: 10.1016/j.isci.2022.104889. eCollection 2022 Sep 16.

Authors

Masakazu Fujii^{1

2

3}, Daiki Setoyama¹, Kazuhito Gotoh¹, Yushi Dozono¹, Mikako Yagi^{1

4}, Masataka Ikeda⁵, Tomomi Ide⁵, Takeshi Uchiumi^{1

4}, Dongchon Kang¹

Affiliations

¹ Department of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
² Department of Internal Medicine, Fukuoka Prefectural Social Insurance Medical Association, Inatsuki Hospital, Kama 820-0207, Japan.
³ Department of Internal Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
⁴ Department of Health Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
⁵ Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.

Abstract

The occurrence of diet-induced obesity has been increasing worldwide and has become a major health concern. Mitochondria are densely distributed in brown adipose tissue and are involved in lipid consumption. Therefore, increasing energy expenditure through the activation of brown adipocytes may be a potential therapy for obesity. Our findings showed that mitochondrial transcription factor A (TFAM) homozygous transgenic (TgTg) mice had highly activated brown adipocytes and increased expression of oxidative phosphorylation, leading to resistance to obesity. Transplantation models of TFAM-expressing brown adipocytes could mimic the phenotype of TFAM TgTg mice, and proving their anti-obesity effect. We found that brown adipocytes secrete exosomes which enable self-activation in an autocrine and paracrine manner. The secretion was enhanced in TFAM TgTg brown adipocytes, resulting in a higher activation. These findings may lead to a promising treatment strategy for obesity through selective stimulation of exosome secretion.

Keywords: Cell biology; Human metabolism; Molecular biology.