Iara Karise1, Thereza Cristina Bargut2, Mariano Del Sol3, Marcia Barbosa Aguila4, Carlos A Mandarim-de-Lacerda5. 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.
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.
Authors: Marta Díaz; Gemma Carreras-Badosa; Joan Villarroya; Aleix Gavaldà-Navarro; Judit Bassols; Francis de Zegher; Abel López-Bermejo; Francesc Villarroya; Lourdes Ibáñez Journal: Pediatr Res Date: 2022-07-11 Impact factor: 3.953
Authors: Sara Cruciani; Giuseppe Garroni; Renzo Pala; Donatella Coradduzza; Maria Laura Cossu; Giorgio Carlo Ginesu; Giampiero Capobianco; Salvatore Dessole; Carlo Ventura; Margherita Maioli Journal: Adipocyte Date: 2022-12 Impact factor: 3.553
Authors: Erica L Underwood; John B Redell; Mark E Maynard; Nobuhide Kobori; Michael J Hylin; Kimberly N Hood; Rebecca K West; Jing Zhao; Anthony N Moore; Pramod K Dash Journal: eNeuro Date: 2022-01-13
Authors: Sara Cruciani; Giuseppe Garroni; Renzo Pala; Maria Laura Cossu; Giorgio Carlo Ginesu; Carlo Ventura; Margherita Maioli Journal: Int J Mol Sci Date: 2021-06-22 Impact factor: 5.923
Authors: Andrew C Shin; Priya Balasubramanian; Pavan Suryadevara; Justin Zyskowski; Thomas H Herdt; Sheba M J MohanKumar; Puliyur S MohanKumar Journal: Int J Obes (Lond) Date: 2020-09-19 Impact factor: 5.095