Cyanidin and malvidin in aqueous extracts of black carrots fermented with Aspergillus oryzae prevent the impairment of energy, lipid and glucose metabolism in estrogen-deficient rats by AMPK activation.

Abstract

Black carrots (Daucus carota L.) are rich in anthocyanins which contribute many health benefits, but are limited by bioavailability and instability when exposed to oxygen, heat and light. Fermenting black carrots may improve the stability, absorption and bioactivity of its anthocyanins. Here, we examined whether and by what mechanisms the long-term consumption of unfermented black carrot extract (BC) and its extracts fermented with Lactobacillus plantarum (BCLP) or Aspergillus oryzae (BCAO) might prevent menopausal symptoms including impaired energy, glucose and lipid metabolism in estrogen-deficient animals with diet-induced obesity. Ovariectomized (OVX) rats were fed four different high-fat diets containing 2% dextrin (OVX-control), 2% BC, 2% BCLP, or 2% BCAO for 12weeks. Sham rats were fed high-fat diets containing 2% dextrin. The contents of total anthocyanins increased in BCAO compared to BC and BCLP, whereas the contents of cyanidin-3-rutinosides, malvidin-3,5-diglycosides and delphine-3-glucoside were lower and cyanidin and malvidin were much higher in BCLP and BCAO than BC. Fat mass and weight gain were lower in descending order of OVX-control>BC and BCLP>BCAO due to increased energy expenditure and fat oxidation. However, BC, BCLP and especially BCAO all normalized HOMA-IR, an indicator of insulin resistance and glucose intolerance, in OVX rats. OVX increased serum total and LDL cholesterol and triglycerides, but BC, BCLP and BCAO significantly prevented the increases. BCAO markedly decreased hepatic triglyceride levels by increasing gene expressions of CPT-1 and PPAR-α, which are involved in fatty acid oxidation, and decreasing mRNA expressions of FAS and SREBP-1c, which are associated with fatty acid synthesis. This was related to increased pAMPK→pACC signaling and improved hepatic insulin signaling (pAkt→pFOXO-1). Cyanidin and malvidin markedly decreased fat accumulation in 3T3-L1 adipocytes by increasing CPT-1 and decreasing FAS and SREBP-1c expression in comparison with cyanidin-3-rutinoside and malvidin-3,5-diglycosides. In conclusion, with increasing cyanidin and malvidin, BCAO prevented the exacerbation of lipid and glucose metabolism by activating hepatic insulin signaling and AMPK activation by in OVX rats.