Follistatin promotes adipocyte differentiation, browning, and energy metabolism

被引:97
作者
Braga, Melissa [1 ]
Reddy, Srinivasa T. [3 ,4 ,5 ]
Vergnes, Laurent [6 ]
Pervin, Shehla [1 ,3 ]
Grijalva, Victor [4 ]
Stout, David [5 ]
David, John [5 ]
Li, Xinmin [6 ]
Tomasian, Venina [6 ]
Reid, Christopher B. [2 ]
Norris, Keith C. [4 ]
Devaskar, Sherin U. [6 ,7 ,8 ]
Reue, Karen
Singh, Rajan [1 ,3 ]
机构
[1] Charles R Drew Univ Med & Sci, Div Endocrinol & Metab, Los Angeles, CA 90059 USA
[2] Charles R Drew Univ Med & Sci, Inst Life Sci, Los Angeles, CA 90059 USA
[3] Univ Calif Los Angeles, David Geffen Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90095 USA
[4] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA
[5] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA
[6] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA
[7] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA
[8] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Los Angeles, CA 90095 USA
基金
美国国家卫生研究院;
关键词
mouse embryonic fibroblast; myostatin; brown fat; energy expenditure; uncoupling protein 1; mitochondria; WHITE ADIPOSE-TISSUE; SKELETAL-MUSCLE; MYOGENIC DIFFERENTIATION; FAT; MOUSE; MYOSTATIN; OBESITY; CELL; GROWTH; PROLIFERATION;
D O I
10.1194/jlr.M039719
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
Follistatin (Fst) functions to bind and neutralize the activity of members of the transforming growth factor-beta superfamily. Fst has a well-established role in skeletal muscle, but we detected significant Fst expression levels in interscapular brown and subcutaneous white adipose tissue, and further investigated its role in adipocyte biology. Fst expression was induced during adipogenic differentiation of mouse brown preadipocytes and mouse embryonic fibroblasts (MEFs) as well as in cold-induced brown adipose tissue from mice. In differentiated MEFs from Fst KO mice, the induction of brown adipocyte proteins including uncoupling protein 1, PR domain containing 16, and PPAR gamma coactivator-1 alpha was attenuated, but could be rescued by treatment with recombinant FST. Furthermore, Fst enhanced thermogenic gene expression in differentiated mouse brown adipocytes and MEF cultures from both WT and Fst KO groups, suggesting that Fst produced by adipocytes may act in a paracrine manner. Our microarray gene expression profiling of WT and Fst KO MEFs during adipogenic differentiation identified several genes implicated in lipid and energy metabolism that were significantly downregulated in Fst KO MEFs. Furthermore, Fst treatment significantly increases cellular respiration in Fst-deficient cells.(jlr) Our results implicate a novel role of Fst in the induction of brown adipocyte character and regulation of energy metabolism.
引用
收藏
页码:375 / 384
页数:10
相关论文
共 49 条
[1]
Brown adipose tissue activity controls triglyceride clearance [J].
Bartelt, Alexander ;
Bruns, Oliver T. ;
Reimer, Rudolph ;
Hohenberg, Heinz ;
Ittrich, Harald ;
Peldschus, Kersten ;
Kaul, Michael G. ;
Tromsdorf, Ulrich I. ;
Weller, Horst ;
Waurisch, Christian ;
Eychmueller, Alexander ;
Gordts, Philip L. S. M. ;
Rinninger, Franz ;
Bruegelmann, Karoline ;
Freund, Barbara ;
Nielsen, Peter ;
Merkel, Martin ;
Heeren, Joerg .
NATURE MEDICINE, 2011, 17 (02) :200-U93
[2]
Nonalcoholic fatty liver disease and vascular risk [J].
Bhatia, Lokpal S. ;
Curzen, Nicholas P. ;
Byrne, Christopher D. .
CURRENT OPINION IN CARDIOLOGY, 2012, 27 (04) :420-428
[3]
Cardiac natriuretic peptides act via p38 MAPK to induce the brown fat thermogenic program in mouse and human adipocytes [J].
Bordicchia, Marica ;
Liu, Dianxin ;
Amri, Ez-Zoubir ;
Ailhaud, Gerard ;
Dessi-Fulgheri, Paolo ;
Zhang, Chaoying ;
Takahashi, Nobuyuki ;
Sarzani, Riccardo ;
Collins, Sheila .
JOURNAL OF CLINICAL INVESTIGATION, 2012, 122 (03) :1022-1036
[4]
Boss Olivier, 2012, Front Endocrinol (Lausanne), V3, P14, DOI 10.3389/fendo.2012.00014
[5]
A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis [J].
Bostroem, Pontus ;
Wu, Jun ;
Jedrychowski, Mark P. ;
Korde, Anisha ;
Ye, Li ;
Lo, James C. ;
Rasbach, Kyle A. ;
Bostroem, Elisabeth Almer ;
Choi, Jang Hyun ;
Long, Jonathan Z. ;
Kajimura, Shingo ;
Zingaretti, Maria Cristina ;
Vind, Birgitte F. ;
Tu, Hua ;
Cinti, Saverio ;
Hojlund, Kurt ;
Gygi, Steven P. ;
Spiegelman, Bruce M. .
NATURE, 2012, 481 (7382) :463-U72
[6]
Inhibition of In Vitro and In Vivo Brown Fat Differentiation Program by Myostatin [J].
Braga, Melissa ;
Pervin, Shehla ;
Norris, Keith ;
Bhasin, Shalender ;
Singh, Rajan .
OBESITY, 2013, 21 (06) :1180-1188
[7]
Testosterone inhibits transforming growth factor-β signaling during myogenic differentiation and proliferation of mouse satellite cells: Potential role of follistatin in mediating testosterone action [J].
Braga, Melissa ;
Bhasin, Shalender ;
Jasuja, Ravi ;
Pervin, Shehla ;
Singh, Rajan .
MOLECULAR AND CELLULAR ENDOCRINOLOGY, 2012, 350 (01) :39-52
[8]
Brown adipose tissue: Function and physiological significance [J].
Cannon, B ;
Nedergaard, J .
PHYSIOLOGICAL REVIEWS, 2004, 84 (01) :277-359
[9]
AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity [J].
Canto, Carles ;
Gerhart-Hines, Zachary ;
Feige, Jerome N. ;
Lagouge, Marie ;
Noriega, Lilia ;
Milne, Jill C. ;
Elliott, Peter J. ;
Puigserver, Pere ;
Auwerx, Johan .
NATURE, 2009, 458 (7241) :1056-U140
[10]
White to Brown Fat Phenotypic Switch Induced by Genetic and Environmental Activation of a Hypothalamic-Adipocyte Axis [J].
Cao, Lei ;
Choi, Eugene Y. ;
Liu, Xianglan ;
Martin, Adam ;
Wang, Chuansong ;
Xu, Xiaohua ;
During, Matthew J. .
CELL METABOLISM, 2011, 14 (03) :324-338