Dietary Betaine Supplementation Increases Fgf21 Levels to Improve Glucose Homeostasis and Reduce Hepatic Lipid Accumulation in Mice
Year: 2016
Type: article
Abstract: Identifying markers of human insulin resistance may permit development of new approaches for treatment and prevention of type 2 diabetes. To this end, we analyzed the fasting plasma metabolome in metabolically characterized human volunteers across a spectrum of insulin resistance. We demonstrate that plasma betaine levels are reduced in insulin-resistant humans and correlate closely with insulin sensitivity. Moreover, betaine administration to mice with diet-induced obesity prevents the development of impaired glucose homeostasis, reduces hepatic lipid accumulation, increases white adipose oxidative capacity, and enhances whole-body energy expenditure. In parallel with these beneficial metabolic effects, betaine supplementation robustly increased hepatic and circulating fibroblast growth factor (Fgf)21 levels. Betaine administration failed to improve glucose homeostasis and liver fat content in Fgf21(-/-) mice, demonstrating that Fgf21 is necessary for betaine's beneficial effects. Together, these data indicate that dietary betaine increases Fgf21 levels to improve metabolic health in mice and suggest that betaine supplementation merits further investigation as a supplement for treatment or prevention of type 2 diabetes in humans.
Source: Diabetes
DOI: 10.2337/db15-1094
Authors: Asma Ejaz, Laura Martinez-Guino, Allison B. Goldfine, Francesc Ribas-Aulinas, Valeria De Nigris, Sílvia Ribó, Alba Gonzalez-Franquesa, Pablo M. Garcia-Roves, Elizabeth Li, Jonathan M. Dreyfuss, Walt Gall, Jason K. Kim, Teodoro Bottiglieri, Francesc Villarroya, Robert E. Gerszten, Mary-Elizabeth Patti, Carles Lerin
Institutions: Joslin Diabetes Center, Harvard University, Hospital Sant Joan de Déu Barcelona, Centro de Investigación Biomédica en Red, Institut de Biomedicina de la Universitat de Barcelona, Universitat de Barcelona, Consorci Institut D'Investigacions Biomediques August Pi I Sunyer, Fundació de Recerca Clínic Barcelona-Institut d’Investigacions Biomèdiques August Pi i Sunyer, Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas, Boston University, Metabolon (United States), University of Massachusetts Chan Medical School, Massachusetts General Hospital
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
Awards: UMass Mouse Metabolic Phenotyping Center, UMass Mouse Metabolic Phenotyping Center, G2037788320, G2833296188, G28897301, G529193044, G5351650593, G5708678602, G5747373093, G643119639, G6728095690, G774051626, G9000005292, G9000056738, Diabetes Research Center, Metabolomic predictors of insulin resistance and diabetes
OpenAlex ID: W2307485186