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

Abstract

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.

Delphinidin Ameliorates Hepatic Triglyceride Accumulation in Human HepG2 Cells, but Not in Diet-Induced Obese Mice

“…Despite this reduction, the energy intake remained similar among groups due to the increase in the proportion of calories from fat in the HFHC diet, as well as the energy from the drinking water. In line with our results, other studies reported similar dietetic patterns, as well as their effect on body weight [ 37 , 38 , 39 ]. C57BL/6J mice on an HFD for 15 weeks gained weight in a comparable way (~44 g of body weight) to that observed herein despite food consumption being lower, and the energy intake was not significantly different compared to those fed with a low-fat diet [ 38 ].…”

Efficacy of an Anthocyanin and Prebiotic Blend on Intestinal Environment in Obese Male and Female Subjects

“…However, studies have demonstrated the positive impact dietary anthocyanins have on microbiota in obese populations which then leads to obesity control, including decreased insulin resistance, decreased inflammation, and decreased fat storage [ 10 ]. Additionally, previous work from our group has demonstrated that a similar anthocyanin blend used in the current clinical study modulated inflammation and improved insulin resistance in high-fat-fed mice [ 47 ].…”

Polyphenols by Generating H2O2, Affect Cell Redox Signaling, Inhibit PTPs and Activate Nrf2 Axis for Adaptation and Cell Surviving: In Vitro, In Vivo and Human Health

“…Many evidences support a potential beneficial action of polyphenols consumption on cardiovascular health [100] and type 2 diabetes mellitus [101,102]. In mice fed a high-fat diet, Daveri et al [103] have shown that polyphenols modulate inflammation and alter redox signaling, improving insulin resistance. Several studies in vivo on tea polyphenols, and especially EGCG, via dampening of PTP1B (protein tyrosine phosphatase 1B) and other PTPs acting as key regulators of tyrosine phosphorylation-dependent signaling accelerate glucose uptake and evoke the IRS-1/Akt/GLUT2 signaling pathway in HepG2 cells and mice liver [104].…”

“…Circulating levels of glucose and free fatty acids are increased in patients with type 2 diabetes mellitus (T2DM) and metabolic syndrome [88,[101][102][103][115][116][117]. These effectors activate the generation of ROS, activation of NF-kB (nuclear factor kappa B) and the pro-inflammatory pathway through phosphatase and NADPH oxidases (NOX1 or NOX4) [96,118,119].…”