Chronic high-sucrose diet increases fibroblast growth factor 21 production and energy expenditure in mice

J Nutr Biochem. 2017 Nov:49:71-79. doi: 10.1016/j.jnutbio.2017.07.010. Epub 2017 Jul 25.

Abstract

Excess carbohydrate intake causes obesity in humans. On the other hand, acute administration of fructose, glucose or sucrose in experimental animals has been shown to increase the plasma concentration of anti-obesity hormones such as glucagon-like peptide 1 (GLP-1) and Fibroblast growth factor 21 (FGF21), which contribute to reducing body weight. However, the secretion and action of GLP-1 and FGF21 in mice chronically fed a high-sucrose diet has not been investigated. To address the role of anti-obesity hormones in response to increased sucrose intake, we analyzed mice fed a high-sucrose diet, a high-starch diet or a normal diet for 15 weeks. Mice fed a high-sucrose diet showed resistance to body weight gain, in comparison with mice fed a high-starch diet or control diet, due to increased energy expenditure. Plasma FGF21 levels were highest among the three groups in mice fed a high-sucrose diet, whereas no significant difference in GLP-1 levels was observed. Expression levels of uncoupling protein 1 (UCP-1), FGF receptor 1c (FGFR1c) and β-klotho (KLB) mRNA in brown adipose tissue were significantly increased in high sucrose-fed mice, suggesting increases in FGF21 sensitivity and energy expenditure. Expression of carbohydrate responsive element binding protein (ChREBP) mRNA in liver and brown adipose tissue was also increased in high sucrose-fed mice. These results indicate that FGF21 production in liver and brown adipose tissue is increased in high-sucrose diet and participates in resistance to weight gain.

Keywords: ChREBP; Energy expenditure; FGF21; GLP-1; Sucrose diet.

MeSH terms

  • Adipose Tissue, Brown / growth & development
  • Adipose Tissue, Brown / metabolism*
  • Adipose Tissue, White / growth & development
  • Adipose Tissue, White / metabolism
  • Animals
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Diet, Carbohydrate Loading / adverse effects*
  • Dietary Sucrose / adverse effects*
  • Energy Metabolism*
  • Fibroblast Growth Factors / agonists*
  • Fibroblast Growth Factors / blood
  • Fibroblast Growth Factors / genetics
  • Fibroblast Growth Factors / metabolism
  • Gene Expression Regulation, Developmental*
  • Insulin Resistance
  • Klotho Proteins
  • Liver / growth & development
  • Liver / metabolism*
  • Male
  • Membrane Proteins / agonists
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice, Inbred C57BL
  • Nuclear Proteins / agonists
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Organ Specificity
  • Receptor, Fibroblast Growth Factor, Type 1 / agonists
  • Receptor, Fibroblast Growth Factor, Type 1 / genetics
  • Receptor, Fibroblast Growth Factor, Type 1 / metabolism
  • Reproducibility of Results
  • Starch / adverse effects
  • Transcription Factors / agonists
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Uncoupling Protein 1 / agonists
  • Uncoupling Protein 1 / genetics
  • Uncoupling Protein 1 / metabolism
  • Weight Gain

Substances

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Dietary Sucrose
  • Klb protein, mouse
  • Membrane Proteins
  • Mlxipl protein, mouse
  • Nuclear Proteins
  • Transcription Factors
  • Ucp1 protein, mouse
  • Uncoupling Protein 1
  • fibroblast growth factor 21
  • Fibroblast Growth Factors
  • Starch
  • Fgfr1 protein, mouse
  • Receptor, Fibroblast Growth Factor, Type 1
  • Klotho Proteins