No abstract

Black currant (Ribes nigrum L.) is a rich source of anthocyanins; however, the relationship between their apparently limited bioavailability and significant protection against metabolic pathologies is poorly understood. This study examined the gastrointestinal distribution of black currant anthocyanins and their phenolic acid metabolites in lean and diet-induced obese mice with healthy and antibiotic-disrupted microbiomes. Daily consumption of low- or high-fat diet supplemented with 1% black currant powdered extract (32% anthocyanins) for 8 weeks reduced body weight gain and improved glucose metabolism only in mice with the intact gut microbiome. Administration of antibiotic cocktail resulted in a 16-25-fold increase (P < 0.001) in anthocyanin content of feces, and cyanidin-based anthocyanins showed the largest increase in fecal content upon disruption of gut microbiome (92.3 ± 16.3 vs 4719 ± 158 μg/g feces), indicating their high susceptibility to microbial degradation in the gut. A 3-fold enrichment (P < 0.05) in gallic over protocatechuic acid was observed in the jejunum of both intact and antibiotic-treated animals, suggesting that this effect was likely independent of their gut microbiome status. Taken together, the data clearly demonstrate that gut microbiome and the type of the anthocyanin aglycone moiety can alter the protective effect of anthocyanins against obesity and associated insulin resistance.

Overconsumption of energy dense foods and sedentary lifestyle are considered as major causes of obesity-associated insulin resistance and abnormal glucose metabolism. Results from both cohort studies and randomized trials suggested that anthocyanins from berries may lower metabolic risks, however these reports are equivocal. The present study was designed to examine effects of six berries with structurally diverse anthocyanin profiles (normalized to 400 µg/g total anthocyanin content) on development of metabolic risk factors in the C57BL/6 mouse model of polygenic obesity. Diets supplemented with blackberry (mono-glycosylated cyanidins), black raspberry (acylated mono-glycosylated cyanidins), blackcurrant (mono- and di-glycosylated cyanidins and delphinidins), maqui berry (di-glycosylated delphinidins), Concord grape (acylated mono-glycosylated delphinidins and petunidins), and blueberry (mono-glycosylated delphinidins, malvidins, and petunidins) showed a prominent discrepancy between biological activities of delphinidin/malvidin-versus cyanidin-type anthocyanins that could be explained by differences in their structure and metabolism in the gut. Consumption of berries also resulted in a strong shift in the gastrointestinal bacterial communities towards obligate anaerobes that correlated with decrease in the gastrointestinal luminal oxygen and oxidative stress. Further work is needed to understand mechanisms that lead to nearly anoxic conditions in the gut lumens, including the relative contributions of host, diet and/or microbial oxidative activity, and their implication to human health.

The steroid hormone 20-hydroxyecdysone (20HE) is an essential signaling molecule that modulates molting response in insects and may function as a putative anabolic factor in vertebrate animals, although no mammalian 20HE receptor has been identified. Here we show that in H4IIE cell culture, 20HE treatment decreased expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase), reduced glucose production, and induced Akt2 phosphorylation sensitive to the phosphoinositide-3 kinase pathway-specific inhibitor LY-294002. Daily oral administration of 20HE (10 mg/kg for 13 wk) ameliorated obesity and insulin resistance in C57BL/6J mice fed a high-fat diet and produced a significant decrease of body weight gain and body fat mass compared with nontreated animals as demonstrated by dual-energy X-ray absorptiometry analysis. In addition, plasma insulin levels and glucose tolerance were significantly lowered by 20HE treatment. These changes were accompanied by the reduced hepatic expression of PEPCK and G6Pase and increased adiponectin production by visceral fat tissue. These studies demonstrate the anti-obesity and anti-diabetic effects of 20HE and begin to elucidate its putative cellular targets both in vitro and in vivo.

Wild lowbush blueberries (Vaccinium angustifolium Ait) are a rich source of anthocyanins and other flavonoids with anti-inflammatory activities; however, their individual effects on cellular signaling remain to be elucidated. This study determined the capacity of blueberry bioactives to protect murine RAW 264.7 macrophages from lipopolysaccharide-induced inflammation. Fractionation of the crude extract (CE) into polyphenol-rich (PPR), anthocyanin-rich (ANC), and proanthocyanidin-rich (PAC) fractions and an ethyl acetate fraction (EA) revealed that PPR, ANC, and PAC components most effectively suppressed mRNA biomarkers of acute inflammation (Cox-2, iNOS, and IL-1β). Among major polyphenols found in the wild blueberries, malvidin-3-glucoside was significantly more effective than epicatechin or chlorogenic acid in reducing the expression of pro-inflammatory genes in vitro.