title: MicroRNA-133 controls brown adipose determination in skeletal muscle satellite cells by targeting Prdm16.
abstract: Brown adipose tissue (BAT) is an energy-dispensing thermogenic tissue that plays an important role in balancing energy metabolism. Lineage-tracing experiments indicate that brown adipocytes are derived from myogenic progenitors during embryonic development. However, adult skeletal muscle stem cells (satellite cells) have long been considered uniformly determined toward the myogenic lineage. Here, we report that adult satellite cells give rise to brown adipocytes and that microRNA-133 regulates the choice between myogenic and brown adipose determination by targeting the 3'UTR of Prdm16. Antagonism of microRNA-133 during muscle regeneration increases uncoupled respiration, glucose uptake, and thermogenesis in local treated muscle and augments whole-body energy expenditure, improves glucose tolerance, and impedes the development of diet-induced obesity. Finally, we demonstrate that miR-133 levels are downregulated in mice exposed to cold, resulting in de novo generation of satellite cell-derived brown adipocytes. Therefore, microRNA-133 represents an important therapeutic target for the treatment of obesity.
authors: Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.
authors: Hang
authors: H
authors: Yin
authors: Alessandra
authors: A
authors: Pasut
authors: Vahab D
authors: VD
authors: Soleimani
authors: C Florian
authors: CF
authors: Bentzinger
authors: Ghadi
authors: G
authors: Antoun
authors: Stephanie
authors: S
authors: Thorn
authors: Patrick
authors: P
authors: Seale
authors: Pasan
authors: P
authors: Fernando
authors: Wilfred
authors: W
authors: van Ijcken
authors: Frank
authors: F
authors: Grosveld
authors: Robert A
authors: RA
authors: Dekemp
authors: Robert
authors: R
authors: Boushel
authors: Mary-Ellen
authors: ME
authors: Harper
authors: Michael A
authors: MA
authors: Rudnicki
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D052437:Adipocytes, Brown / Q000166:cytology; D002001:Adipose Tissue, Brown / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D003080:Cold Temperature; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics; D004734:Energy Metabolism; D005951:Glucose Tolerance Test; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D039902:Multipotent Stem Cells / Q000166:cytology; D012038:Regeneration / Q000235:genetics; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D004268:DNA-Binding Proteins; D035683:MicroRNAs; C517732:Mirn133 microRNA, mouse; C521133:Prdm16 protein, mouse; D014157:Transcription Factors
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