Red wine compounds have been reported to reduce the rate of atherosclerosis by inducing nitric oxide (NO) production and antioxidant enzyme expression in vascular endothelial cells (VECs). The present study compared the effects of the three red wine compounds resveratrol and its dimers, ε-viniferin and δ-viniferin, on VECs function for the first time. Both 5 μM ε-viniferin and δ-viniferin, but not 5 μM resveratrol, significantly stimulated wound repair of VECs. Increased levels of wound repair induced by 10 and 20 μM ε-viniferin were significantly higher than those stimulated by 10 and 20 μM resveratrol, respectively. These stimulatory effects of the three compounds were suppressed by the NO synthase inhibitor L-NAME. When VECs were exposed to each compound, endothelial NO synthase was activated and the expression of sirtuin 1 (SIRT1) and HO-1 was induced. Addition of the SIRT1 and HO-1 inhibitors EX527 and ZnPPiX, respectively, suppressed wound repair stimulated by the three compounds, demonstrating that SIRT1 and HO-1 are involved in these wound repair processes. Furthermore, each compound induced the suppression of H 2 O 2-dependent reduction of cell viability as well as the expression of the antioxidant enzyme catalase. These data suggest that not only resveratrol, but also its dimers, ε-viniferin and δ-viniferin, may be effective in preventing atherosclerosis by a similar molecular mechanism with different potency and efficacy.

Rodent studies that measure effects of dietary components on the microbiome generally use basal diets such as the AIN diet series which is formulated with purified ingredients and has nutrient profile that optimizes growth and fertility and poorly models human intakes. Previously, we used NHANES data to formulate the Total Western Diet (TWD), a rodent diet that emulates average American intake levels for macro and micronutrients using nutrient density. However, the TWD is comprised of purified ingredients and does not recapitulate the complex food matrix consumed by Americans. Using the latest version of the USDA Food Intakes Converted to Retail Commodities Database, we modified the TWD by using the most commonly consumed whole foods as dietary ingredients. The TWD2 has the same micro and macronutrient content as the previous TWD but contains 25 food ingredients including: sweeteners (sucrose and high fructose corn syrup); flours (wheat, potato, corn, rice and oat); meats (beef, poultry, pork, eggs and fish); dairy (lactose, whey and casein); fruits/vegetables (oranges, apples, bananas, grapes, strawberries, soy, snap beans, peanuts and cashews). To test whether the Western dietary pattern and/or the food matrix affected the microbiome, mice were fed for 15 weeks either: AIN93‐G, TWD, TWD2 or TWD‐F (TWD matched for total fiber to TWD2). Bacterial DNA from fecal samples harvested at sacrifice was extracted and microbiome composition was determined by 16s sequencing. Bacteriodetes was the majority phylum in mice fed the whole food TWD2 while Firmicutes was the majority phylum in all other treatments formulated with purified ingredients. Other notable phylum level differences included a significant increase in Proteobacteria (P < 0.05) in TWD2 fed mice compared to the other treatments and increased Tenericutes in AIN93‐G fed mice compared to the other treatments (P < 0.05). TWD2 fed mice had a significantly more diverse microbiome compared to all treatments except the TWDF (observed operational taxonomic units, P < 0.05). Lastly, beta diversity analysis revealed that TWD2 fed mice clustered apart from all other treatments as measured by principle coordinates analysis. Our data suggests that a diet with a complex food matrix, compared to purified diets induces profound changes in the microbiome even when macro and micronutrient contents are the same.Support or Funding InformationFunding provided by the Utah Agricultural Experiment Station

Rodent studies that test the effects of bioactive dietary components on chronic disease generally use purified basal diets that were established using nutrient profiles optimized for growth and fertility such as the AIN93‐G diet which is not reflective of typical American macro and micronutrient intake. Previously, we used NHANES data to formulate the Total Western Diet (TWD), a rodent diet that emulates average American intake levels for macro and micronutrients using nutrient density. We have demonstrated that the TWD increases basal colorectal cancer (CRC) by ~2‐fold compared to the standard AIN93‐G diet in three different models. However, the TWD is comprised of purified ingredients and does not recapitulate the complex food matrix consumed by Americans. Using the latest version of the USDA Food Intakes Converted to Retail Commodities Database, we modified the TWD by using the most commonly consumed whole foods as dietary ingredients. The TWD2 has the same micro and macronutrient content as the previous TWD but contains 25 food ingredients including: sweeteners (sucrose and high fructose corn syrup); flours (wheat, potato, corn, rice and oat); meats (beef, poultry, pork, eggs and fish); dairy (lactose, whey and casein); fruits/vegetables (oranges, apples, bananas, grapes, strawberries, soy, snap beans, peanuts and cashews). To test whether food matrix affected CRC outcome, mice were fed either: AIN93‐G, TWD, TWD2 or TWD‐F (TWD matched for total fiber to TWD2). Mice were initiated with 10 mg/kg azoxymethane (AOM) and provided 1% dextran sodium sulfate (DSS) in their drinking water for 4 weeks to promote colonic inflammation and tumorigenesis. Necropsy and tumor assessment was performed after 15 weeks of treatment. A cohort of sham mice were fed the same diets but not injected with AOM or given DSS to determine effect of diets on metabolism and the gut microbiome. Mice fed the TWD, TWD‐F, and TWD2 did not differ in colon tumor multiplicity but all had significantly more tumors than mice fed the AIN93‐G diet (P < 0.01). Interestingly, mice fed the TWD2 diet consumed significantly more energy and gained more weight than all other treatments (P < 0.05). TWD2 fed mice also had significantly higher total fat mass, body fat percentage, and total visceral fat mass than AIN93‐G fed mice (P < 0.05) but not the purified TWD treatments. Lastly, TWD2 fed mice had significantly higher blood glucose concentrations than AIN93‐G fed mice, but not mice fed the purified TWD diets, at 90 and 120 minutes after oral glucose challenge (P < 0.05). Our data suggests that a diet with a complex food matrix, compared to purified diets with the same macro and micronutrient content, does not influence CRC but does increase energy consumption, adiposity, and glucose intolerance.Support or Funding InformationUtah Agricultural Experiment Station