Metabolic effects of basic fibroblast growth factor in streptozotocin-induced diabetic rats: A 1H NMR-based metabolomics investigation

Sci Rep. 2016 Nov 3:6:36474. doi: 10.1038/srep36474.

Abstract

The fibroblast growth factors (FGFs) family shows a great potential in the treatment of diabetes, but little attention is paid to basic FGF (bFGF). In this study, to explore the metabolic effects of bFGF on diabetes, metabolic changes in serum and feces were analyzed in the normal rats, the streptozocin (STZ)-induced diabetic rats and the bFGF-treated diabetic rats using a 1H nuclear magnetic resonance (NMR)-based metabolomic approach. Interestingly, bFGF treatment significantly decreased glucose, lipid and low density lipoprotein/very low density lipoprotein (LDL/VLDL) levels in serum of diabetic rats. Moreover, bFGF treatment corrected diabetes-induced reductions in citrate, lactate, choline, glycine, creatine, histidine, phenylalanine, tyrosine and glutamine in serum. Fecal propionate was significantly increased after bFGF treatment. Correlation analysis shows that glucose, lipid and LDL/VLDL were significantly negatively correlated with energy metabolites (citrate, creatine and lactate) and amino acids (alanine, glycine, histidine, phenylalanine, tyrosine and glutamine). In addition, a weak but significant correlation was observed between fecal propionate and serum lipid (R = -0.35, P = 0.046). Based on metabolic correlation and pathway analysis, therefore, we suggest that the glucose and lipid lowering effects of bFGF in the STZ-induced diabetic rats may be achieved by activating microbial metabolism, increasing energy metabolism and correcting amino acid metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / blood
  • Animals
  • Blood Glucose / analysis
  • Choline / blood
  • Citric Acid / blood
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetes Mellitus, Experimental / pathology*
  • Discriminant Analysis
  • Down-Regulation / drug effects
  • Feces / chemistry
  • Fibroblast Growth Factor 2 / genetics
  • Fibroblast Growth Factor 2 / pharmacology*
  • Fibroblast Growth Factor 2 / therapeutic use
  • Humans
  • Lactic Acid / blood
  • Least-Squares Analysis
  • Lipoproteins, LDL / blood
  • Male
  • Metabolome / drug effects*
  • Metabolomics*
  • Proton Magnetic Resonance Spectroscopy
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / pharmacology
  • Recombinant Proteins / therapeutic use
  • Streptozocin / toxicity
  • Up-Regulation / drug effects

Substances

  • Amino Acids
  • Blood Glucose
  • Lipoproteins, LDL
  • Recombinant Proteins
  • Fibroblast Growth Factor 2
  • Citric Acid
  • Lactic Acid
  • Streptozocin
  • Choline