title: Mitochondrial Activity in Human White Adipocytes Is Regulated by the Ubiquitin Carrier Protein 9/microRNA-30a Axis.
abstract: The acquisition of beige adipocyte features by white fat cells corresponds to protection against obesity-induced metabolic diseases in humans and animal models of type 2 diabetes. In adipose tissue, expression of the E2 small ubiquitin-like modifier ligase ubiquitin carrier protein 9 (Ubc9) is positively correlated with markers of insulin resistance and corresponds with impaired browning of human white adipocytes. However, the molecular regulation of Ubc9 expression in adipocytes and other cells remains unclear. In this study, we demonstrate that the mRNA and protein expression of Ubc9 are regulated by the microRNA miRNA-30a (miR-30a) in human subcutaneous adipocytes. Ubc9 and miR-30a exhibit inverse expression in adipose tissue, with miR-30a robustly elevated in brown fat. Depletion of Ubc9 by siRNA or enforced expression of a miR-30a mimic augments mitochondrial volume and respiration in human white adipocytes, reflecting features of brown fat cells. Furthermore, Ubc9 depletion induces a brown fat gene program in human subcutaneous adipocytes. Induction of the beige-selective gene program corresponds to stabilization of the PR domain-containing 16 (PRDM16) protein, an obligate transcriptional regulator of the brown/beige fat metabolic program in white adipocytes that interacts with Ubc9. Taken together, our data demonstrate a previously unappreciated molecular axis that controls browning of human white adipocytes.
authors.affiliation: From the Departments of Molecular and Cellular Biology and; the Department of Internal Medicine, Asan Medical Center, Seoul 138-736, Republic of Korea.
authors.forename: Eun Hee
authors.initials: EH
authors.lastname: Koh
authors.affiliation: the Diabetes Center and Department of Cell and Tissue Biology, University of California, San Francisco, California 94143, and.
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: From the Departments of Molecular and Cellular Biology and.
authors.forename: David A
authors.initials: DA
authors.lastname: Bader
authors.affiliation: From the Departments of Molecular and Cellular Biology and.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Hamilton
authors.affiliation: From the Departments of Molecular and Cellular Biology and; Medicine, Division of Hematology and Oncology, Baylor College of Medicine, Houston, Texas 77030.
authors.forename: Bin
authors.initials: B
authors.lastname: He
authors.affiliation: From the Departments of Molecular and Cellular Biology and.
authors.forename: Brian
authors.initials: B
authors.lastname: York
authors.affiliation: the Diabetes Center and Department of Cell and Tissue Biology, University of California, San Francisco, California 94143, and.
authors.forename: Shingo
authors.initials: S
authors.lastname: Kajimura
authors.affiliation: From the Departments of Molecular and Cellular Biology and; the Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030.
authors.forename: Sean E
authors.initials: SE
authors.lastname: McGuire
authors.affiliation: From the Departments of Molecular and Cellular Biology and. Electronic address: hartig@bcm.edu.
authors.forename: Sean M
authors.initials: SM
authors.lastname: Hartig
mesh_terms: D052438:Adipocytes, White / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis*; D008928:Mitochondria / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes / Q000096:biosynthesis*; D000098843:Ubiquitin-Conjugating Enzyme UBC9
chemical_list: D004268:DNA-Binding Proteins; C546086:MIRN30b microRNA, human; D035683:MicroRNAs; C416371:PRDM16 protein, human; D014157:Transcription Factors; D044763:Ubiquitin-Conjugating Enzymes; D000098843:Ubiquitin-Conjugating Enzyme UBC9
keywords: adipose tissue metabolism; bioenergetics; gene transcription; microRNA (miRNA); mitochondria; posttranscriptional regulation; respiration; tissue-specific transcription factor; transcription coregulator; transcription target gene