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Blockade of the activin receptor IIb activates functional brown adipogenesis and thermogenesis by inducing mitochondrial oxidative metabolism.
- Source :
-
Molecular and cellular biology [Mol Cell Biol] 2012 Jul; Vol. 32 (14), pp. 2871-9. Date of Electronic Publication: 2012 May 14. - Publication Year :
- 2012
-
Abstract
- Brown adipose tissue (BAT) is a key tissue for energy expenditure via fat and glucose oxidation for thermogenesis. In this study, we demonstrate that the myostatin/activin receptor IIB (ActRIIB) pathway, which serves as an important negative regulator of muscle growth, is also a negative regulator of brown adipocyte differentiation. In parallel to the anticipated hypertrophy of skeletal muscle, the pharmacological inhibition of ActRIIB in mice, using a neutralizing antibody, increases the amount of BAT without directly affecting white adipose tissue. Mechanistically, inhibition of ActRIIB inhibits Smad3 signaling and activates the expression of myoglobin and PGC-1 coregulators in brown adipocytes. Consequently, ActRIIB blockade in brown adipose tissue enhances mitochondrial function and uncoupled respiration, translating into beneficial functional consequences, including enhanced cold tolerance and increased energy expenditure. Importantly, ActRIIB inhibition enhanced energy expenditure only at ambient temperature or in the cold and not at thermoneutrality, where nonshivering thermogenesis is minimal, strongly suggesting that brown fat activation plays a prominent role in the metabolic actions of ActRIIB inhibition.
- Subjects :
- Activin Receptors, Type II immunology
Activin Receptors, Type II metabolism
Adipocytes, Brown cytology
Adipocytes, Brown metabolism
Adipose Tissue, Brown ultrastructure
Animals
Antibodies, Neutralizing
Cell Differentiation
Energy Metabolism
Female
Male
Mice
Mice, Inbred C57BL
Mice, SCID
Mice, Transgenic
Microscopy, Electron, Transmission
Mitochondria metabolism
Muscle, Skeletal metabolism
Myostatin metabolism
Signal Transduction
Smad3 Protein metabolism
Transcription Factors metabolism
Activin Receptors, Type II antagonists & inhibitors
Adipogenesis physiology
Adipose Tissue, Brown metabolism
Thermogenesis physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1098-5549
- Volume :
- 32
- Issue :
- 14
- Database :
- MEDLINE
- Journal :
- Molecular and cellular biology
- Publication Type :
- Academic Journal
- Accession number :
- 22586266
- Full Text :
- https://doi.org/10.1128/MCB.06575-11