title: Manipulating molecular switches in brown adipocytes and their precursors: a therapeutic potential.
abstract: Brown adipocytes constitute a metabolically active tissue responsible for non-shivering thermogenesis and the depletion of excess calories. Differentiation of brown fat adipocytes de novo or stimulation of pre-existing brown adipocytes within white adipose depots could provide a novel method for reducing the obesity and alleviating the consequences of type II diabetes worldwide. In this review, we addressed several molecular mechanisms involved in the control of brown fat activity, namely, the β₃-adrenergic stimulation of thermogenesis during exposure to cold or by catecholamines; the augmentation of thyroid function; the modulation of peroxisome proliferator-activated receptor gamma (PPARγ), transcription factors of the C/EBP family, and the PPARγ co-activator PRDM16; the COX-2-driven expression of UCP1; the stimulation of the vanilloid subfamily receptor TRPV1 by capsaicin and monoacylglycerols; the effects of BMP7 or its analogs; the cannabinoid receptor antagonists and melanogenesis modulating agents. Manipulating one or more of these pathways may provide a solution to the problem of harnessing brown fat's thermogenic potential. However, a better understanding of their interplay and other homeostatic mechanisms is required for the development of novel therapies for millions of obese and/or diabetic individuals.
authors.affiliation: Center for the Study of Chronic Metabolic Diseases, School of Systems Biology, College of Science, George Mason University, Fairfax, VA, USA.
authors.forename: Aybike
authors.initials: A
authors.lastname: Birerdinc
authors.forename: Mohammed
authors.initials: M
authors.lastname: Jarrar
authors.forename: Tim
authors.initials: T
authors.lastname: Stotish
authors.forename: Manpreet
authors.initials: M
authors.lastname: Randhawa
authors.forename: Ancha
authors.initials: A
authors.lastname: Baranova
mesh_terms: D000222:Adaptation, Physiological; D052437:Adipocytes, Brown / Q000187:drug effects* / Q000502:physiology*; D002001:Adipose Tissue, Brown / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D000818:Animals; D055419:Bone Morphogenetic Protein 7 / Q000378:metabolism; D063387:Cannabinoid Receptor Antagonists / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D002395:Catecholamines / Q000378:metabolism; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D007473:Ion Channels / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D043882:Receptors, Cannabinoid / Q000378:metabolism; D022722:Thermogenesis; D013963:Thyroid Hormones / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D000071256:Uncoupling Protein 1
chemical_list: C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; D063387:Cannabinoid Receptor Antagonists; D002395:Catecholamines; D004268:DNA-Binding Proteins; D007473:Ion Channels; D024101:Mitochondrial Proteins; D047495:PPAR gamma; C416371:PRDM16 protein, human; D043882:Receptors, Cannabinoid; D013963:Thyroid Hormones; D014157:Transcription Factors; C000604371:UCP1 protein, human; D000071256:Uncoupling Protein 1; D002211:Capsaicin