Gooseberry anthocyanins alleviate insulin resistance by regulating ceramide metabolism in high fat diet mice

Background/aim: Obesity is the fifth largest risk factor of death in the world. The ceramide produced by obesity is closely related to insulin resistance (IR) caused by obesity. At present, the commercially available weight loss products have large side effects and limited therapeutic effects. Therefore, it is particularly important to find effective natural nontoxic products to treat obesity and explore its possible pathways and mechanisms. Materials and methods: In this paper, a high-fat diet (HFD) mice model was established by intragastric administration of high-fat emulsion to investigate the intervention effect of Gooseberry anthocyanins (GA) on IR in HFD mice. We used molecular docking technology to find the binding sites and binding energy of anthocyanins on CerS6. Real-time PCR was used to detect the effect of GA on the expression of IL-6 and TNF-α mRNA in HFD mice. The expression of S1P/Cer signaling pathway in HFD mice with IR was detected by Western Blot. Results: The results showed that GA could effectively inhibit visceral fat, liver index, the level of TC, TG and the level of LDL-C (p < 0.05), and improved HDL-C, GSH-Px and SOD (p < 0.05). GA decreased the level of insulin sensitivity index from -5.15 to -4.54 and improved insulin sensitivity and IR in HFD mice. The binding energy of anthocyanins on CerS6 was in the range of -8.2 to 5.2 kcal/ mol, with low energy parameters and good binding positions. GA could reduce mRNA levels of inflammatory factors IL-6 and TNF-α (p < 0.05), inhibit the expression of CerS6, PKCζ, PPARγ, CD36 (p < 0.05), and enhance the expression of SphK2, Akt, p-Akt/Akt, ISR (p < 0.05). Conclusion: This study investigated the effect and mechanism of GA on reducing ceramide content and reducing IR in mice, and provided an experimental basis for the prevention and treatment of obesity-related diseases.