Malvidin-3-<i>O</i>-glucoside and Malvidin-3,5-<i>O</i>-diglucoside Alleviate Glycolipid Metabolic Disorder by Modulating Pancreas and Liver Functions and Gut Microbiota

The anthocyanins malvidin-3-<i>O</i>-glucoside (M3G) and malvidin-3,5-<i>O</i>-diglucoside (M35G) were purified from the grape varieties <i>Vitis vinifera</i> L. and <i>Vitis davidii</i> Foex peels, respectively, and their effects on glycolipid metabolic disorders (GLMDs) were investigated using a mouse model. Mice treated with M3G or M35G showed controlled body weight, preservation of normal histomorphological features and islet size of the pancreas, and amelioration of hyperglycemia and insulin resistance induced by a high-fructose diet. M35G was more effective than M3G in improving insulin sensitivity, lipid homeostasis, and adipocyte hypertrophy. Moreover, M3G and M35G regulated hepatic genes (e.g., ketohexokinase, phosphoenolpyruvate carboxykinase, fatty acid synthase, and carbohydrate response element binding protein-beta) to restrain GLMD development. Furthermore, the inhibition of hepatic inflammation and oxidative stress and the modulation of the abundance of probiotic microbial genera synergistically improved physiological indices and prevented GLMD development.