Studies On The Anti-obesity Effect And Mechanisms Of Pitaya Betacyanins

Obesity is characterized by impaired energy metabolism and excessive fat accumulation, attributed to a complex interaction between genetic background and lifestyles, such as dietary and sedentary habits. Moreover, obesity can lead to various complications, such as insulin resistance, type 2 diabetes, hyperlipemia, hypertension, nonalcoholic fatty liver disease and cardiovascular disease. Traditional obesity management approaches exist many limitations, such as side effects and secondary failure.As natural and edible pigments, betalains have been extensively used as colorants in the food industry. Increasing evidence indicates that betalains possess free radical-scavenging and antioxidant activities, which are closely associated with the protective effects of betalains against inflammation, high blood pressure, atherosclerosis and hyperlipidemia. It’s important to investigate the potential effects of pitaya betacyanins on obesity.In this context, we identified the varieties of betacyanins present in Hylocereus undatus (white pitaya) peel and Hylocereus polyrhizus (red pitaya) fruit by liquid chromatography-mass spectrometry analysis, investigated the protective effects of betacyanins against oleic acid (OA)-induced simple lipid accumulation in HepG2 cells and explored the potential molecular mechanisms, focusing on the role of autophagy in liver protection. We also evaluated the influences of pitaya juice and betacyanins on obesity and its metabolic disorders, including insulin resistance and hepatic steatosis in high-fat diet-induced obese mice, and determined whether the beneficial effects of betacyanins were associated with the improved lipid metabolism and modulation of gut microbiota. The main findings of the research were as follows:1. Though administration of white pitaya juice (WPJ) failed to decrease diet-induced body weight gain in mice, it significantly decreased serum TG, TC, glucose and LDL-C and hepatic TG and TC levels, improved high-fat diet (HFD)-induced insulin resistance, hepatic steatosis and adipose hypertrophy. Hepatic gene expression analysis showed that WPJ supplement not only changed the expression profile of genes involved in lipid and cholesterol metabolism but also significantly increased the expression levels of FGF2/-related genes, indicating that the beneficial effects of WPJ was associated with the improved FGF21 resistance and lipid metabolism.2. Our results showed that the white fleshed pitaya peel contains 14 kinds of betacyanins, while red fleshed pitaya fruit contains 12 kinds of betacyanins. Moreover, both of them possess free radical scavenging and antioxidant capacity.3. Dietary Hylocereus undatus peel betacyanins (PPBN) and HPBN could reduce HFD-induced body weight gain, decreased serum TG, TC, glucose and LDL-C and hepatic TG and TC levels, attenuated high-fat diet (HFD)-induced insulin resistance, hepatic steatosis and adipose hypertrophy and improved glucose intolerance, and PPBN was more effective than HPBN. Moreover, the hepatic gene expression analysis indicated that PPBN supplementation changed the expression profiles of lipid metabolism-related genes and FGF21-related genes, suggesting that the protective effect of PPBN might be associated with the induced fatty acid oxidation, decreased fatty acid biosynthesis and alleviated FGF21 resistance.16S rDNA analysis indicated that HPBN could alter the gut microbiota community, especially it could decrease the ratio of Firmicutes, increase the ratio of Bacteroidetes and Proteobacteria in the phylum level, and increased the relative abundance of Akkermansia in the genus level.4. Our results showed that Hylocereus polyrhizus fruit betacyanins (HPBN) decreased OA-induced lipid accumulation. Immunofluorescence and westernblot analysis showed that HPBN treatment increased the autophagy-related protein level of LC3B-II, Beclinl and Atg7, and the transmission electron microscopy analysis showed that HPBN treatment resulted in numerous autophagocytic vacuoles, indicating that autophagy was activated in HPBN-treated cells. Incubation with autophagy inhibitor (3-MA) markedly attenuated HPBN-induced steatosis improvement. These data indicated that HPBN treatment significantly improved OA-induced steatosis in hepatocytes, and this protective effect was partially mediated by enhanced autophagy.