Fujii Masakazu, Setoyama Daiki, Gotoh Kazuhito, Dozono Yushi, Yagi Mikako, Ikeda Masataka, Ide Tomomi, Uchiumi Takeshi, Kang Dongchon
Department of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Department of Internal Medicine, Fukuoka Prefectural Social Insurance Medical Association, Inatsuki Hospital, Kama 820-0207, Japan.
iScience. 2022 Aug 10;25(9):104889. doi: 10.1016/j.isci.2022.104889. eCollection 2022 Sep 16.
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.
饮食诱导的肥胖在全球范围内呈上升趋势，已成为一个主要的健康问题。线粒体密集分布于棕色脂肪组织中，并参与脂质消耗。因此，通过激活棕色脂肪细胞来增加能量消耗可能是一种治疗肥胖的潜在方法。我们的研究结果表明，线粒体转录因子A（TFAM）纯合转基因（TgTg）小鼠的棕色脂肪细胞高度活化，氧化磷酸化表达增加，从而产生抗肥胖作用。表达TFAM的棕色脂肪细胞移植模型可模拟TFAM TgTg小鼠的表型，证实其抗肥胖作用。我们发现棕色脂肪细胞分泌外泌体，这些外泌体能够以自分泌和旁分泌方式实现自我激活。TFAM TgTg棕色脂肪细胞中外泌体的分泌增强，导致更高的激活水平。这些发现可能会带来一种通过选择性刺激外泌体分泌来治疗肥胖的有前景的策略。
