スギモト　ケン   Ken Sugimoto   杉本　研    所属   川崎医科大学  医学部 臨床医学　総合老年医学    職種   教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Novel properties of myoferlin in glucose metabolism via pathways involving modulation of adipose functions.
掲載誌名	正式名：FASEB journal : official publication of the Federation of American Societies for Experimental Biology 略　 称：FASEB J ISSNコード：15306860/08926638
掲載区分	国外
巻・号・頁	34(2),pp.2792-2811
著者・共著者	Nozato Yoichi, Takami Yoichi, Yamamoto Koichi, Nagasawa Motonori, Nozato Satoko, Imaizumi Yuki, Takeshita Hikari, Wang Cheng, Ito Yuki, Takeda Shuko, Takeya Yasushi, Sugimoto Ken, Nakagami Hironori, Hanayama Rikinari, Rakugi Hiromi
発行年月	2020/02
概要	While adipose tissue is required to maintain glucose metabolism, excessive calorie intake induces obesity via mechanisms including accelerated proliferation and differentiation of preadipocytes, leading to insulin resistance. Here, we investigated the role of myoferlin (MYOF), a ferlin family protein, in regulating glucose metabolism by mainly focusing on its unknown role in adipose tissue. Whereas young MYOF knockout (KO) mice on a normal diet showed aggravated glucose tolerance and insulin sensitivity, those on a high-fat diet (HFD) showed preserved glucose tolerance with an attenuated gain of body weight, reduced visceral fat deposits, and less severe fatty liver. The Adipose MYOF expression was reduced by aging but was restored by an HFD along with the retained expression of NFAT transcription factors. Loss-of-function of MYOF in preadipocytes suppressed proliferation and differentiation into mature adipocytes along with the decreased expression of genes involved in adipogenesis. The MYOF expression in preadipocytes was reduced with differentiation. Attenuated obesity in MYOF KO mice on an HFD was also accompanied with increased oxygen consumption by an unidentified mechanism and with reduced adipose inflammation due to less inflammatory macrophages. These insights suggest that the multifunctional roles of MYOF involve the regulation of preadipocyte function and affect glucose metabolism bidirectionally depending on consumed calories.
DOI	10.1096/fj.201901539RR
PMID	31912559