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

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.

Repurposing of Anti-Diabetic Agents as a New Opportunity to Alleviate Cognitive Impairment in Neurodegenerative and Neuropsychiatric Disorders

“…Sulforaphane is a compound with multiple bioactivities such as antidiabetic and antioxidant effects. Sulforaphane could improve glucose tolerance through up-regulation of insulin signaling involving IRS-1/Akt/GLUT 4 pathway in muscle( Xu et al, 2018 ). Sulforaphane also attenuated glucose intolerance and affected GLUT3 expression in the cerebral cortex and hypothalamus( Souza et al, 2013 ).…”

Comparative Effects of Sulforaphane and Allyl Isothiocyanate on 3T3-L1 Adipogenesis

“…However, Ernst et al [ 9 ] reported that treatment with sulforaphane and other ITCs, such as allyl isothiocyanate, results in comparative levels of phase 2 enzymes including γ -glutamyl cysteine synthetase and antioxidant enzymes via an Nrf2-dependent signal transduction pathway in cultured cells and in vivo experiments. Conversely, Valli et al [ 10 ] and Xu et al [ 11 ] demonstrated that sulforaphane-treated obese mice exhibited significantly increased IRS-1 protein levels and marked Akt/PKB activation. Comparison of IRS-1 upregulation by sulforaphane and other ITCs, including allyl isothiocyanate, will require additional investigation.…”

“…Allyl isothiocyanate (Figure 1) is known to be responsible for the characteristic pungent aroma of some cruciferous vegetables, including radishes and horse radishes. Both of these are naturally occurring ITCs repress adipogenesis [9][10][11]. However, with the exception of their ITC moieties, the pharmacological differences caused by their distinct structures-the sulfinyl groups in sulforaphane and the allyl groups in allyl isothiocyanate-have not been investigated.…”

Interventions to Address Environmental Metabolism-Disrupting Chemicals: Changing the Narrative to Empower Action to Restore Metabolic Health

“…Brassica crops (e.g., cabbage, broccoli, cauliflower, kale, collards, and brussel sprouts) contain chemicals that release sulforaphane upon hydrolysis. Sulphoraphane has been shown to help reduce obesity (131), improve glucose tolerance (132), and restore leptin sensitivity in high fat-sucrose diet fed obese mice (133). Sulforaphane functions by protecting against oxidative stress via activation of the Nrf2-ARE pathway in multiple tissues (134, 135).…”