Metformin enhances mitochondrial biogenesis and thermogenesis in brown adipocytes of mice

Biomed Pharmacother. 2019 Mar;111:1156-1165. doi: 10.1016/j.biopha.2019.01.021. Epub 2019 Jan 12.
Metformin enhances mitochondrial biogenesis and thermogenesis in brown adipocytes of mice.
Karise I1, Bargut TC2, Del Sol M3, Aguila MB4, Mandarim-de-Lacerda CA5.
Author information
1
Laboratory of Morphometry, Metabolism and Cardiovascular Disease, Biomedical Center, Institute of Biology, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address: iarakarise@hotmail.com.
2
Laboratory of Morphometry, Metabolism and Cardiovascular Disease, Biomedical Center, Institute of Biology, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address: therezabargut@gmail.com.
3
Doctoral Program in Morphological Sciences, Universidad de La Frontera, Temuco, Chile. Electronic address: mariano.delsol@ufrontera.cl.
4
Laboratory of Morphometry, Metabolism and Cardiovascular Disease, Biomedical Center, Institute of Biology, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address: mbaguila@uerj.br.
5
Laboratory of Morphometry, Metabolism and Cardiovascular Disease, Biomedical Center, Institute of Biology, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address: mandarim@uerj.br.
Abstract
AIMS:
We studied the effect of metformin on the brown adipose tissue (BAT) in a fructose-rich-fed model, focusing on BAT proliferation, differentiation, and thermogenic markers.

MAIN METHODS:
C57Bl/6 mice received isoenergetic diets for ten weeks: control (C) or high-fructose (F). For additional eight weeks, animals received metformin hydrochloride (M, 250 mg/kg/day) or saline. After sacrifice, BAT and white fat pads were prepared for light microscopy and molecular analyses.

KEY FINDINGS:
Body mass gain, white fat pads, and adiposity index were not different among the groups. There was a reduction in energy intake in the F group and energy expenditure in the F and FM groups. Metformin led to a more massive BAT in both groups CM and FM, associated with a higher adipocyte proliferation (β1-adrenergic receptor, proliferating cell nuclear antigen, and vascular endothelial growth factor), and differentiation (PR domain containing 16, bone morphogenetic protein 7), in part by activating 5' adenosine monophosphate-activated protein kinase. Metformin also enhanced thermogenic markers in the BAT (uncoupling protein type 1, peroxisome proliferator-activated receptor gamma coactivator-1 alpha) through adrenergic stimuli and fibroblast growth factor 21. Metformin might improve mitochondrial biogenesis in the BAT (nuclear respiratory factor 1, mitochondrial transcription factor A), lipolysis (perilipin, adipose triglyceride lipase, hormone-sensitive lipase), and fatty acid uptake (lipoprotein lipase, cluster of differentiation 36, adipocyte protein 2).

SIGNIFICANCE:
Metformin effects are not linked to body mass changes, but affect BAT thermogenesis, mitochondrial biogenesis, and fatty acid uptake. Therefore, BAT may be a metformin adjuvant target for the treatment of metabolic disorders.

Copyright © 2019 Elsevier Masson SAS. All rights reserved.

KEYWORDS:
Brown adipose tissue; Fructose; Metformin; Mouse; Thermogenesis

Metformin enhances mitochondrial biogenesis and thermogenesis in brown adipocytes of mice. - PubMed - NCBI
https://www.ncbi.nlm.nih.gov/pubmed/30841429