miR-107 inhibits CDK6 expression, differentiation, and lipid storage in human adipocytes.

Abstract

MicroRNA-107 (miR-107) plays a regulatory role in obesity and insulin resistance, but the mechanisms of its function in adipocytes have not been elucidated in detail. Here we show that overexpression of miR-107 in pre- and mature human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes attenuates differentiation and lipid accumulation. Our results suggest that miR-107 controls adipocyte differentiation via CDK6 and Notch signaling. CDK6 is a validated target of miR-107 and was downregulated upon miR-107 overexpression. Notch3, a signaling receptor involved in adipocyte differentiation, has been shown to decrease upon CDK6 depletion; Here Notch3 and its target Hes1 were downregulated by miR-107 overexpression. In mature adipocytes, miR-107 induces a triglyceride storage defect by impairing glucose uptake and triglyceride synthesis. To conclude, our data suggests that miR-107 has distinct functional roles in preadipocytes and mature adipocytes; Its elevated expression at these different stages of adipocytes may on one hand dampen adipogenesis, and on the other, promote ectopic fatty acid accumulation and reduced glucose tolerance.

• Authors: Maria A Ahonen, P A Nidhina Haridas, Raghavendra Mysore, Martin Wabitsch, Pamela Fischer-Posovszky, Vesa M Olkkonen
• Journal: Molecular and cellular endocrinology (Mol Cell Endocrinol) Vol. 479 Pg. 110-116 (01 05 2019) ISSN: 1872-8057 [Electronic] Ireland
• PMID: 30261211 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 Elsevier B.V. All rights reserved.

Chemical References

• MIRN107 microRNA, human
• MicroRNAs
• Receptors, Notch
• Transcription Factor HES-1
• Triglycerides
• HES1 protein, human
• CDK6 protein, human
• Cyclin-Dependent Kinase 6
• Glucose

Topics

• Adipocytes (cytology, metabolism)
• Cell Differentiation (genetics)
• Cell Line
• Cyclin-Dependent Kinase 6 (genetics, metabolism)
• Down-Regulation (genetics)
• Glucose (metabolism)
• Humans
• Inflammation (genetics)
• Lipid Droplets (metabolism)
• Lipid Metabolism (genetics)
• MicroRNAs (genetics, metabolism)
• Models, Biological
• Receptors, Notch (metabolism)
• Transcription Factor HES-1 (genetics, metabolism)
• Triglycerides (metabolism)