Format

Send to

Choose Destination
Mol Metab. 2016 Jun 15;5(8):615-625. doi: 10.1016/j.molmet.2016.06.005. eCollection 2016 Aug.

miR-125b affects mitochondrial biogenesis and impairs brite adipocyte formation and function.

Author information

1
Univ. Nice Sophia Antipolis, CNRS, Inserm, iBV, 06100 Nice, France.
2
Department of Phoniatrics, ENT University Hospital, Medical University Graz, Graz, Austria.
3
Inserm, UMR1048, Obesity Research Laboratory, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France; University of Toulouse, UMR1048, Paul Sabatier University, Toulouse, France.
4
Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, D-89075 Ulm, Germany.
5
Department of General and Visceral Surgery, Ulm University Surgery Center, D-89075 Ulm, Germany.
6
Department of Endocrinology, Turku University Hospital, Turku, 20521, Finland.
7
Department of Endocrinology, Turku University Hospital, Turku, 20521, Finland; Turku University Hospital, Turku, Finland.
8
Institute for Diabetes and Cancer (IDC), Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Joint Heidelberg-IDC Translational Diabetes Program, Heidelberg University Hospital, Heidelberg, Germany; Molecular Metabolic Control, Medical Faculty, Technical University Munich, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany.
9
Department of Endocrinology, Turku University Hospital, Turku, 20521, Finland; Turku PET Centre, University of Turku, Turku, Finland.
10
Inserm, UMR1048, Obesity Research Laboratory, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France; University of Toulouse, UMR1048, Paul Sabatier University, Toulouse, France; Toulouse University Hospitals, Department of Clinical Biochemistry, Toulouse, France.
11
Univ. Nice Sophia Antipolis, CNRS, Inserm, iBV, 06100 Nice, France. Electronic address: amri@unice.fr.

Abstract

OBJECTIVE:

In rodents and humans, besides brown adipose tissue (BAT), islands of thermogenic adipocytes, termed "brite" (brown-in-white) or beige adipocytes, emerge within white adipose tissue (WAT) after cold exposure or β3-adrenoceptor stimulation, which may protect from obesity and associated diseases. microRNAs are novel modulators of adipose tissue development and function. The purpose of this work was to characterize the role of microRNAs in the control of brite adipocyte formation.

METHODS/RESULTS:

Using human multipotent adipose derived stem cells, we identified miR-125b-5p as downregulated upon brite adipocyte formation. In humans and rodents, miR-125b-5p expression was lower in BAT than in WAT. In vitro, overexpression and knockdown of miR-125b-5p decreased and increased mitochondrial biogenesis, respectively. In vivo, miR-125b-5p levels were downregulated in subcutaneous WAT and interscapular BAT upon β3-adrenergic receptor stimulation. Injections of an miR-125b-5p mimic and LNA inhibitor directly into WAT inhibited and increased β3-adrenoceptor-mediated induction of UCP1, respectively, and mitochondrial brite adipocyte marker expression and mitochondriogenesis.

CONCLUSION:

Collectively, our results demonstrate that miR-125b-5p plays an important role in the repression of brite adipocyte function by modulating oxygen consumption and mitochondrial gene expression.

KEYWORDS:

Brite adipocyte; Mitochondriogenesis; White adipocyte; miR-125b-5p

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center