Direct conversion of human fibroblasts to brown adipocytes by small chemical compounds

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K15222
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Dai Ping 京都府立医科大学, 医学(系)研究科(研究院), 准教授 (20291924)
• Co-Investigator(Kenkyū-buntansha): 武田 行正 京都府立医科大学, 医学(系)研究科(研究院), 助教 (40735552)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: ダイレクトリプログラミング / 褐色脂肪細胞 / 細胞移植治療 / 再生医療 / 低分子化合物

Outline of Final Research Achievements

Brown adipocytes maintain body temperature by burning lipid, which can prevent obese and diabetes by enhancing energy expenditure. Brown adipocytes are differentiated from induced pluripotent stem cells (iPSCs) and directly converted from fibroblasts by virus vector-mediated expression of a specific set of transcription factors. In order to provide a safer approach to generate brown adipocytes, we developed chemical compound-based direct conversion from human dermal fibroblasts into brown adipocytes without any genetic manipulation. The chemical compound-induced brown adipocytes (ciBAs) exhibit expression of human brown adipocyte-specific genes including Ucp1, activation of thermogenic gene expression through adrenergic receptor, and increased oxygen consumption rates. Our findings might provide an easily accessible approach for generating human brown adipocytes from fibroblasts and offer therapeutic potential for the management of obesity, diabetes, and related metabolic disorders.

Free Research Field

再生医学