Dietary Betaine Supplementation Increases Fgf21 Levels to Improve Glucose Homeostasis and Reduce Hepatic Lipid Accumulation in Mice

Diabetes. 2016 Apr;65(4):902-12. doi: 10.2337/db15-1094. Epub 2016 Feb 8.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Betaine / pharmacology*
  • Cells, Cultured
  • Dietary Supplements
  • Fatty Liver / chemically induced
  • Fatty Liver / drug therapy
  • Fatty Liver / genetics
  • Fatty Liver / metabolism
  • Female
  • Fibroblast Growth Factors / blood*
  • Fibroblast Growth Factors / genetics
  • Glucose / metabolism*
  • Glucose Intolerance / blood
  • Glucose Intolerance / drug therapy
  • Homeostasis / drug effects
  • Homeostasis / genetics
  • Humans
  • Lipid Metabolism / drug effects*
  • Liver / drug effects*
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout

Substances

  • fibroblast growth factor 21
  • Betaine
  • Fibroblast Growth Factors
  • Glucose