オクニシ　カツヒデ   Okunishi Katsuhide   奥西　勝秀    所属   東邦大学  医学部 医学科    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	Insulin Regulates Lipolysis and Fat Mass by Upregulating Growth/Differentiation Factor 3 in Adipose Tissue Macrophages.
掲載誌名	正式名：Diabetes ISSNコード：0012-1797
掲載区分	国外
巻・号・頁	67(9),pp.1761-1772
著者・共著者	Yun Bu,Katsuhide Okunishi,Satomi Yogosawa,Kouichi Mizuno,Maria Johnson Irudayam,Chester W Brown,Tetsuro Izumi
発行年月	2018/09
概要	Previous genetic studies in mice have shown that functional loss of activin receptor-like kinase 7 (ALK7), a type I transforming growth factor-β receptor, increases lipolysis to resist fat accumulation in adipocytes. Although growth/differentiation factor 3 (GDF3) has been suggested to function as a ligand of ALK7 under nutrient-excess conditions, it is unknown how GDF3 production is regulated. Here, we show that a physiologically low level of insulin converts CD11c- adipose tissue macrophages (ATMs) into GDF3-producing CD11c+ macrophages ex vivo and directs ALK7-dependent accumulation of fat in vivo. Depletion of ATMs by clodronate upregulates adipose lipases and reduces fat mass in ALK7-intact obese mice, but not in their ALK7-deficient counterparts. Furthermore, depletion of ATMs or transplantation of GDF3-deficient bone marrow negates the in vivo effects of insulin on both lipolysis and fat accumulation in ALK7-intact mice. The GDF3-ALK7 axis between ATMs and adipocytes represents a previously unrecognized mechanism by which insulin regulates both fat metabolism and mass.
DOI	10.2337/db17-1201
PMID	29945891