Cyanidin and delphinidin modulate inflammation and altered redox signaling improving insulin resistance in high fat-fed mice

Consumption of diets high in fat and/or fructose content promotes tissue inflammation, oxidative stress, and insulin resistance, activating signals (e.g. NF-κB/JNK) that downregulate the insulin cascade. Current evidence supports the concept that select flavonoids can mitigate obesity and type 2 diabetes (T2D). This work investigated if supplementation with the anthocyanidins (AC) cyanidin and delphinidin could attenuate the adverse consequences of consuming a high fat diet (HFD) in mice. Consumption of an AC-rich blend mitigated HFD-induced obesity, dyslipidemia and insulin resistance (impaired responses to insulin and glucose). HFD-fed mice were characterized by increased liver lipid deposition and inflammation, which were also attenuated upon AC supplementation. HFD caused liver oxidative stress showing an increased expression of NADPH oxidases, generators of superoxide and H2O2, and high levels of oxidized lipid-protein adducts. This was associated with the activation of the redox sensitive signals IKK/NF-κB and JNK1/2, and increased expression of the NF-κB-regulated PTP1B phosphatase, all known inhibitors of the insulin pathway. In agreement with an improved insulin sensitivity, AC supplementation inhibited oxidative stress, NF-κB and JNK activation, and PTP1B overexpression. Thus, cyanidin and delphinidin consumption either through diet or by supplementation could be a positive strategy to control the adverse effects of Western style diets, including overweight, obesity, and T2D. Modulation of inflammation, oxidative stress, and NF-κB/JNK activation emerge as relevant targets of AC beneficial actions.Fil: Daveri, Elena. University of California. Department of Nutrition and Department of Environmental Toxicology; Estados UnidosFil: Cremonini, Eleonora. University of California. Department of Nutrition and Department of Environmental Toxicology; Estados UnidosFil: Mastaloudis, Angela. Nse Products, Inc.; Estados UnidosFil: Hester, Shelly N.. Nse Products, Inc.; Estados UnidosFil: Wood, Steven M.. Nse Products, Inc.; Estados UnidosFil: Waterhouse, Andrew L.. University of California; Estados UnidosFil: Anderson, Mauri. University of California; Estados UnidosFil: Fraga, César Guillermo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Analitica y Fisicoquímica. Cátedra de Fisicoquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Oteiza, Patricia Isabel. University of California. Department of Nutrition and Department of Environmental Toxicology; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin