Ken Sugimoto    Department   Kawasaki Medical School  Kawasaki Medical School, Department of General Geriatric Medicine,    Position   Professor
Article types	原著
Language	English
Peer review	Peer reviewed
Title	Novel properties of myoferlin in glucose metabolism via pathways involving modulation of adipose functions.
Journal	Formal name：FASEB journal : official publication of the Federation of American Societies for Experimental Biology Abbreviation：FASEB J ISSN code：15306860/08926638
Domestic / Foregin	Foregin
Volume, Issue, Page	34(2),pp.2792-2811
Author and coauthor	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
Publication date	2020/02
Summary	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