Several reports have demonstrated that cerebral blood flow decreases with age and may contribute to neurodegenerative changes found in aging animals and man. Because GH and insulin-like growth factor 1 (IGF-1) decrease with age and have an important role in vascular maintenance and remodeling, we hypothesized that the decrease in cerebral blood flow is associated with a rarefaction of cerebral blood vessels resulting from a decline in GH and IGF-1. Measurements of vascular density (number of vessels/cortical surface area) in both Brown-Norway and Fisher 344/Brown-Norway rats were made at 5, 13, and 29 months of age using chronic cranial window chambers that allowed viewing of the cortical surface and its corresponding vasculature. Correlations were made with plasma levels of IGF-1. In Brown-Norway rats, arteriolar density decreased from 15.53 +/- 1.08 to 9.49 +/- 0.62 endpoints/mm2 in 7- and 29-month-old animals, respectively (P < 0.05). A decline was observed also in arteriolar anastomoses [3.05 +/- 0.21 to 1.42 +/- 0.24 connections/mm2 in 7- and 29-month-old animals (P< 0.05)]. Venular density did not decrease with age. Similar changes were observed in Fisher 344/Brown-Norway rats. The number of cortical surface arterioles was correlated with plasma IGF-1 levels at the time of vascular mapping (r = 0.772, P < 0.05), and injection of bovine GH (0.25 mg/kg, s.c., twice daily for 35 days) to 30-month-old animals increased both plasma IGF-1 and the number of cortical arterioles. These data indicate that: 1) vascular density on the surface of the cortex decreases with age; 2) vascular density is correlated with plasma levels of IGF-1; and 3) injection of GH increases cortical vascular density in older animals. We conclude that GH and IGF-1 have an important role in the decline in vascular density with age and suggest that decreases in vascular density may have important implications for the age-related decline in cerebral blood flow and brain function.

The objective of this study was to determine if consuming an extractable or non-extractable fraction of table grapes reduced the metabolic consequences of consuming a high-fat, American-type diet. Male C57BL/6J mice were fed a low fat (LF) diet, a high fat (HF) diet, or a HF diet containing whole table grape powder (5% w/w), an extractable, polyphenol-rich (HF-EP) fraction, a non-extractable, polyphenol-poor (HF-NEP) fraction, or equal combinations of both fractions (HF-EP+NEP) from grape powder for 16 weeks. Mice fed the HF-EP and HF-EP+NEP diets had lower percentages of body fat and amounts of white adipose tissue (WAT) and improved glucose tolerance compared to the HF-fed controls. Mice fed the HF-EP+NEP diet had lower liver weights and triglyceride (TG) levels compared to the HF-fed controls. Mice fed the HF-EP+NEP diets had higher hepatic mRNA levels of hormone sensitive lipase and adipose TG lipase, and decreased expression of c-reactive protein compared to the HF-fed controls. In epididymal (visceral) WAT, the expression levels of several inflammatory genes were lower in mice fed the HF-EP and HF-EP+NEP diets compared to the HF-fed controls. Mice fed the HF diets had increased myeloperoxidase activity and impaired localization of the tight junction protein zonula occludens-1 in ileal mucosa compared to the HF-EP and HF-NEP diets. Several of these treatment effects were associated with alterations in gut bacterial community structure. Collectively, these data demonstrate that the polyphenol-rich, EP fraction from table grapes attenuated many of the adverse health consequences associated with consuming a HF diet.

Our objective was to determine if consuming table grapes reduces adiposity and its metabolic consequences and alters gut microbiota in mice fed a high fat (HF), butter-rich diet. C57BL/6J mice were fed a low fat (LF) diet or HF diet with 3% or 5% grapes for 11 weeks. Total body and inguinal fat were moderately, but significantly reduced in mice fed both levels of grapes compared to their controls. Mice fed 5% grapes had lower liver weights and triglyceride levels, and decreased expression of glycerol-3-phosphate acyltransferase (Gpat1) compared to the 5% controls. Mice fed 3% grapes had lower hepatic mRNA levels of peroxisome proliferator-activated receptor gamma 2, sterol-CoA desaturase 1, fatty-acid binding protein 4, and Gpat1 compared to the 3% controls. Although grape feeding had only a minor impact on markers of inflammation or lipogenesis in adipose tissue or intestine, 3% grapes decreased the intestinal abundance of sulfidogenic Desulfobacter spp., and the Bilophila wadsworthia-specific dissimilatory sulfite reductase gene (dsrA-Bw), and tended to increase the abundance of the beneficial bacterium Akkermansia muciniphila compared to controls. Additionally, Bifidobacterium, Lactobacillus, Allobaculum, and several other genera correlated negatively with adiposity. Allobaculum in particular was increased in the LF and 3% grapes groups compared to the HF-fed controls. Notably, grape feeding attenuated the HF-induced impairment in epithelial localization of the intestinal tight junction protein zonula occludens. Collectively, these data indicate that some of the adverse health consequences of consuming a HF diet rich in saturated fat can be attenuated by table grape consumption.

No abstract