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: Eun Hee Koh, Yong Chen, David A Bader, Mark P Hamilton, Bin He, Brian York, Shingo Kajimura, Sean E McGuire, Sean M Hartig
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 291 Issue 47 Pg. 24747-24755 (Nov 18 2016) ISSN: 1083-351X [Electronic] United States
• PMID: 27758866 (Publication Type: Journal Article)
• Copyright: © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Chemical References

• DNA-Binding Proteins
• MIRN30b microRNA, human
• MicroRNAs
• PRDM16 protein, human
• Transcription Factors
• Ubiquitin-Conjugating Enzymes
• ubiquitin-conjugating enzyme UBC9

Topics

• Adipocytes, White (cytology, metabolism)
• Animals
• DNA-Binding Proteins (metabolism)
• Gene Expression Regulation (physiology)
• Humans
• Male
• Mice
• MicroRNAs (biosynthesis)
• Mitochondria (metabolism)
• Transcription Factors (metabolism)
• Ubiquitin-Conjugating Enzymes (biosynthesis)