Sulforaphane ameliorates glucose intolerance in obese mice via the upregulation of the insulin signaling pathway

Food Funct. 2018 Sep 19;9(9):4695-4701. doi: 10.1039/c8fo00763b.

Abstract

Sulforaphane (SFN) is a dietary component with multiple bioactivities; however, its role in obesity-related metabolic derangement remains unclear. Here, the effect of SFN on the glucose intolerance of obese mice and the underlying mechanism were determined. C57B/6J male mice were randomly divided into two groups, having free access to water and a normal-fat diet (ND, n = 6) or a high-fat diet (HFD, n = 33) for 8 weeks; thereafter twelve mice having the greatest weight gain among the HFD-fed mice were considered as obese mice. These obese mice were randomly divided into two groups and treated orally for 6 weeks with or without SFN (100 μmol per kg bw, 3 times per week). During this period the animals were continuously maintained on a ND or a HFD. Blood glucose and serum insulin were examined; then glucose tolerance and insulin resistance were evaluated. In addition, the expression of insulin signaling pathway-related genes in the muscle was determined. Our data showed that the obese mice presented a marked insulin resistance and glucose intolerance as compared to the control group, while SFN treatment exerted a prominently protective effect. In addition, the SFN-treated obese mice had a significantly increased insulin receptor substrate 1 (IRS-1) protein level (P < 0.05), markedly elevated Akt activation, as well as dramatically enhanced phosphorylation of PDK-1 (P < 0.05) when compared with the SFN-untreated obese mice. Moreover, the SFN-treated obese mice exhibited a significantly enhanced translocation of GLUT4 (P < 0.05) to the plasma membrane in the muscle compared to the obese mice without SFN treatment. In conclusion, our results support the notion that SFN acts as a promising agent to improve glucose tolerance through the up-regulation of insulin signaling mainly involving the IRS-1/Akt/GLUT4 pathway in the muscle.

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Diet, High-Fat / adverse effects
  • Glucose Intolerance / drug therapy*
  • Glucose Intolerance / genetics
  • Glucose Intolerance / metabolism
  • Glucose Transporter Type 4 / genetics
  • Glucose Transporter Type 4 / metabolism
  • Humans
  • Insulin / genetics
  • Insulin / metabolism*
  • Insulin Receptor Substrate Proteins / genetics
  • Insulin Receptor Substrate Proteins / metabolism
  • Isothiocyanates / administration & dosage*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Obese
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • Signal Transduction / drug effects
  • Up-Regulation / drug effects

Substances

  • Blood Glucose
  • Glucose Transporter Type 4
  • Insulin
  • Insulin Receptor Substrate Proteins
  • Isothiocyanates
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • sulforaphane