title: Sulforaphane Protects against High Cholesterol-Induced Mitochondrial Bioenergetics Impairments, Inflammation, and Oxidative Stress and Preserves Pancreaticβ-Cells Function.
abstract: Cholesterol plays an important role in inducing pancreaticβ-cell dysfunction, leading to an impaired insulin secretory response to glucose. This study aimed to determine the protective effects of sulforaphane, a natural isothiocyanate Nrf2-inducer, against cholesterol-induced pancreaticβ-cells dysfunction, through molecular and cellular mechanisms involving mitochondrial bioenergetics. Sulforaphane prevented cholesterol-induced alterations in the coupling efficiency of mitochondrial respiration, improving ATP turnover and spare capacity, and averted the impairment of the electron flow at complexes I, II, and IV. Sulforaphane also attenuated the cholesterol-induced activation of the NFκB pathway, normalizing the expression of pro- and anti-inflammatory cytokines. In addition, it also inhibited the decrease insirtuin 1expression and greatly increasedPgc-1αexpression in Min6 cells. Sulforaphane increased the expression of antioxidant enzymes downstream of the Nrf2 pathway and prevented lipid peroxidation induced by cholesterol. The antioxidant and anti-inflammatory properties of sulforaphane and its ability to protect and improve mitochondrial bioenergetic function contribute to its protective action against cholesterol-induced pancreaticβ-cell dysfunction. Our data provide a scientifically tested foundation upon which sulforaphane can be developed as nutraceutical to preserveβ-cell function and eventually control hyperglycemia.
authors.affiliation: Department of Nutrition, Faculty of Medicine, University of Chile, P.O. Box 8380453, Santiago, Chile; School of Biomedical Sciences, The University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: Catalina
authors.identifier: 0000-0002-2029-2114
authors.initials: C
authors.lastname: Carrasco-Pozo
authors.affiliation: School of Biomedical Sciences, The University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: Kah Ni
authors.initials: KN
authors.lastname: Tan
authors.affiliation: Department of Nutrition, Faculty of Medicine, University of Chile, P.O. Box 8380453, Santiago, Chile; Institute of Nutrition and Food Technology, University of Chile, P.O. Box 138-11, Santiago, Chile.
authors.forename: Martin
authors.initials: M
authors.lastname: Gotteland
authors.affiliation: School of Biomedical Sciences, The University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: Karin
authors.identifier: 0000-0001-7448-0770
authors.initials: K
authors.lastname: Borges
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D002478:Cells, Cultured; D002784:Cholesterol / Q000633:toxicity*; D019587:Dietary Supplements; D004734:Energy Metabolism / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects; D066298:In Vitro Techniques; D007249:Inflammation; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D017879:Isothiocyanates / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D013454:Sulfoxides
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D017879:Isothiocyanates; D013454:Sulfoxides; D002784:Cholesterol; C016766:sulforaphane