Myocardin-Related Transcription Factor A Regulates Conversion of Progenitors to Beige Adipocytes

被引：125

作者：

McDonald, Meghan E. ^{[1
]}

Li, Chendi ^{[1
]}

Bian, Hejiao ^{[1
]}

Smith, Barbara D. ^{[1
]}

Layne, Matthew D. ^{[1
]}

Farmer, Stephen R. ^{[1
]}

机构：

[1] Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA

来源：

CELL | 2015年 / 160卷 / 1-2期

关键词：

WHITE ADIPOSE-TISSUE; BONE MORPHOGENETIC PROTEIN-7; ACTIN GENE-EXPRESSION; SMOOTH-MUSCLE-CELLS; GAMMA PPAR-GAMMA; BROWN ADIPOCYTES; STEM-CELLS; TRANSFORMING GROWTH-FACTOR-BETA-1; SKELETAL-MUSCLE; FAT;

D O I：

10.1016/j.cell.2014.12.005

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Adipose tissue is an essential regulator of metabolic homeostasis. In contrast with white adipose tissue, which stores excess energy in the form of triglycerides, brown adipose tissue is thermogenic, dissipating energy as heat via the unique expression of the mitochondrial uncoupling protein UCP1. A subset of UCP1+ adipocytes develops within white adipose tissue in response to physiological stimuli; however, the developmental origin of these "brite'' or "beige'' adipocytes is unclear. Here, we report the identification of a BMP7-ROCK signaling axis regulating beige adipocyte formation via control of the G-actin-regulated transcriptional coactivator myocardin-related transcription factor A, MRTFA. White adipose tissue from MRTFA(-/-) mice contains more multilocular adipocytes and expresses enhanced levels of brown-selective proteins, including UCP1. MRTFA(-/-) mice also show improved metabolic profiles and protection from diet-induced obesity and insulin resistance. Our study hence unravels a central pathway driving the development of physiologically functional beige adipocytes.

引用

页码：105 / 118

页数：14

共 87 条

[1] PPARγ signaling and metabolism: the good, the bad and the future [J].

Ahmadian, Maryam ;

Suh, Jae Myoung ;

Hah, Nasun ;

Liddle, Christopher ;

Atkins, Annette R. ;

Downes, Michael ;

Evans, Ronald M. .

NATURE MEDICINE, 2013, 19 (05) :557-566

[2] EXPRESSION OF HUMAN BONE MORPHOGENETIC PROTEINS-2 OR PROTEINS-4 IN MURINE MESENCHYMAL PROGENITOR C3H10T1/2 CELLS INDUCES DIFFERENTIATION INTO DISTINCT MESENCHYMAL CELL LINEAGES [J].

AHRENS, M ;

ANKENBAUER, T ;

SCHRODER, D ;

HOLLNAGEL, A ;

MAYER, H ;

GROSS, G .

DNA AND CELL BIOLOGY, 1993, 12 (10) :871-880

[3] β-catenin activation is necessary and sufficient to specify the dorsal dermal fate in the mouse [J].

Atit, Radhika ;

Sgaier, Sema K. ;

Mohamed, Othman A. ;

Taketo, Makoto M. ;

Dufort, Daniel ;

Joyner, Alexandra L. ;

Niswander, Lee ;

Conlon, Ronald A. .

DEVELOPMENTAL BIOLOGY, 2006, 296 (01) :164-176

[4] The emergence of cold-induced brown adipocytes in mouse white fat depots is determined predominantly by white to brown adipocyte transdifferentiation [J].

Barbatelli, G. ;

Murano, I. ;

Madsen, L. ;

Hao, Q. ;

Jimenez, M. ;

Kristiansen, K. ;

Giacobino, J. P. ;

De Matteis, R. ;

Cinti, S. .

AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2010, 298 (06) :E1244-E1253

[5] 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

[6] 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

[7] A role for bone morphogenetic protein-4 in adipocyte development [J].

Bowers, Robert R. ;

Lane, M. Daniel .

CELL CYCLE, 2007, 6 (04) :385-389

[8] Brown adipose tissue: Function and physiological significance [J].

Cannon, B ;

Nedergaard, J .

PHYSIOLOGICAL REVIEWS, 2004, 84 (01) :277-359

[9] Identification of a CArG-independent region of the cysteine-rich protein 2 promoter that directs expression in the developing vasculature [J].

Chang, YF ;

Wei, J ;

Liu, XL ;

Chen, YH ;

Layne, MD ;

Yet, SF .

AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2003, 285 (04) :H1675-H1683

[10] Transforming growth factor-β inhibits adipocyte differentiation by Smad3 interacting with CCAAT/enhancer-binding protein (C/EBP) and repressing C/EBP transactivation function [J].

Choy, L ;

Derynck, R .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (11) :9609-9619

← 1 2 3 4 5 6 7 8 9 →