Dietary Betaine Supplementation Increases Fgf21 Levels to Improve Glucose Homeostasis and Reduce Hepatic Lipid Accumulation in Mice
Por:
Ejaz A, Martínez-Guino L, Goldfine AB, Ribas-Aulinas F, De Nigris V, Ribó-Gené S, Gonzalez-Franquesa A, Garcia-Roves PM, Li E, Dreyfuss JM, Gall W, Kim JK, Bottiglieri T, Villarroya-Gombau F, Gerszten RE, Patti ME and Lerin C
Publicada:
1 abr 2016
Resumen:
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.
Filiaciones:
Ejaz A:
Research Division, Joslin Diabetes Center, and Harvard Medical School, Boston, MA
Martínez-Guino L:
Endocrinology Section, Hospital Sant Joan de Déu, Barcelona, Spain
Goldfine AB:
Research Division, Joslin Diabetes Center, and Harvard Medical School, Boston, MA
Ribas-Aulinas F:
Department of Biochemistry and Molecular Biology, Institute of Biomedicine, University of Barcelona, and CIBER Fisiopatología de la Obesidad y Nutrición, Barcelona, Spain
De Nigris V:
Diabetes and Obesity Laboratory, Institut d'Investigacions Biomèdiques August Pi Sunyer, Barcelona, Spain
Ribó-Gené S:
Endocrinology Section, Hospital Sant Joan de Déu, Barcelona, Spain
Gonzalez-Franquesa A:
Diabetes and Obesity Laboratory, Institut d'Investigacions Biomèdiques August Pi Sunyer, Barcelona, Spain
Garcia-Roves PM:
Diabetes and Obesity Laboratory, Institut d'Investigacions Biomèdiques August Pi Sunyer, Barcelona, Spain CIBERDEM, Barcelona, Spain Department of Physiological Sciences II, University of Barcelona, Barcelona, Spain
Li E:
Research Division, Joslin Diabetes Center, and Harvard Medical School, Boston, MA
Dreyfuss JM:
Research Division, Joslin Diabetes Center, and Harvard Medical School, Boston, MA Department of Biomedical Engineering, Boston University, Boston, MA
Gall W:
Metabolon, Inc., Durham, NC
Kim JK:
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA
Bottiglieri T:
Institute of Metabolic Disease, Baylor Research Institute, Dallas, TX
Villarroya-Gombau F:
Department of Biochemistry and Molecular Biology, Institute of Biomedicine, University of Barcelona, and CIBER Fisiopatología de la Obesidad y Nutrición, Barcelona, Spain
Gerszten RE:
Massachusetts General Hospital and Harvard Medical School, Boston, MA
Green Submitted, Bronze
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