Emerging roles for the transforming growth factor-{beta} superfamily in regulating adiposity and energy expenditure. 2011

Nader Zamani, and Chester W Brown
Baylor College of Medicine, Houston, Texas 77030, USA.

Members of the TGF-β superfamily regulate many aspects of development, including adipogenesis. Studies in cells and animal models have characterized the effects of superfamily signaling on adipocyte development, adiposity, and energy expenditure. Although bone morphogenetic protein (BMP) 4 is generally considered a protein that promotes the differentiation of white adipocytes, BMP7 has emerged as a selective regulator of brown adipogenesis. Conversely, TGF-β and activin A inhibit adipocyte development, a process augmented in TGF-β-treated cells by Smads 6 and 7, negative regulators of canonical TGF-β signaling. Other superfamily members have mixed effects on adipogenesis depending on cell culture conditions, the timing of expression, and the cell type, and many of these effects occur by altering the expression or activities of proteins that control the adipogenic cascade, including members of the CCAAT/enhancer binding protein family and peroxisome proliferator-activated receptor-γ. BMP7, growth differentiation factor (GDF) 8, and GDF3 are versatile in their mechanisms of action, and altering their normal expression characteristics has significant effects on adiposity in vivo. In addition to their roles in adipogenesis, activins and BMP7 regulate energy expenditure by affecting the expression of genes that contribute to mitochondrial biogenesis and function. GDF8 signals through its own receptors during adipogenesis while antagonizing BMP7, an example of a ligand from one major branch of the superfamily regulating the other. With such intricate relationships that ultimately affect adiposity, TGF-β superfamily signaling holds considerable promise as a target for treating human obesity and its comorbidities.

UI MeSH Term Description Entries
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D004734 Energy Metabolism The chemical reactions involved in the production and utilization of various forms of energy in cells. Bioenergetics,Energy Expenditure,Bioenergetic,Energy Expenditures,Energy Metabolisms,Expenditure, Energy,Expenditures, Energy,Metabolism, Energy,Metabolisms, Energy
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D016212 Transforming Growth Factor beta A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGF-beta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins. Bone-Derived Transforming Growth Factor,Platelet Transforming Growth Factor,TGF-beta,Milk Growth Factor,TGFbeta,Bone Derived Transforming Growth Factor,Factor, Milk Growth,Growth Factor, Milk
D050156 Adipogenesis The differentiation of pre-adipocytes into mature ADIPOCYTES. Adipogeneses
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D028341 Activins Activins are produced in the pituitary, gonads, and other tissues. By acting locally, they stimulate pituitary FSH secretion and have diverse effects on cell differentiation and embryonic development. Activins are glycoproteins that are hetero- or homodimers of INHIBIN-BETA SUBUNITS. Activin,FSH-Releasing Protein,FSH Releasing Protein,Protein, FSH-Releasing

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