With a positive caloric balance, adipocytes undergo excessive hypertrophy, which causes adipocyte dysfunction, as well as adipose tissue endocrine and immune responses. A preferential site of fat accumulation is the abdominal-perivisceral region, due to peculiar factors of the adipose tissue in such sites, namely an excess of glucocorticoid activity, which promotes the accumulation of fat; and the greater metabolic activity and sensitivity to lipolysis, due to increased number and activity of β3-adrenoceptors and, partly, to reduced activity of α2-adrenoceptors. As a consequence, more free fatty acids (FFA) are released into the portal system. Hypertrophic adipocytes begin to secrete low levels of TNF-α, which stimulate preadipocytes and endothelial cells to produce MCP-1, in turn responsible for attracting macrophages to the adipose tissue, thus developing a state of chronic low-grade inflammation which is causally linked to insulin resistance. Excess of circulating FFA, TNF-α and other factors induces insulin resistance. FFA cause insulin resistance by inhibiting insulin signaling through the activation of serin-kinases, i.e. protein kinase C-Θ, and the kinases JNK and IKK, which promote a mechanism of serine phosphorylation of Insulin Receptor Substrates (IRS), leading to interruption of the downstream insulin receptor (IR) signaling. TNF-α, secreted by hypertrophic adipocytes and adipose tissue macrophages, also inhibits IR signaling by a double mechanism of serine-phosphorylation and tyrosine-dephosphorylation of IRS-1, causing inactivation and degradation of IRS-1 and a consequent stop of IR signaling. Such mechanisms explain the transition from excess adiposity to insulin resistance, key to the further development of type 2 diabetes

We investigated the relationship of metabolic syndrome (MetS) and its individual components with incidence of mild cognitive impairment (MCI) and its progression to dementia in a large longitudinal Italian population-based sample with a 3.5-year follow-up. A total of 2097 participants from a sample of 5632 65-84-year-old subjects from the Italian Longitudinal Study on Aging were evaluated. MetS was defined according to the Third Adults Treatment Panel of the National Cholesterol Education Program criteria. MCI, dementia, Alzheimer's disease (AD), and vascular dementia (VaD) were classified using current published criteria. Among MCI patients those with MetS (N=49) had a higher risk of progression to dementia (HR, 4.40; 95% CI, 1.30-14.82) compared with those without MetS (N=72). After a multivariate adjustment, the risk in MCI patients with MetS approximately doubled (multivariate adjusted HR, 7.80, 95% CI 1.29-47.20) compared with those MCI without MetS. Finally, among non-cognitively impaired individuals there were no significant differences in risks of developing MCI in those who were affected by MetS (N=608) in comparison with those without MetS (N=837), as well as excluding those individuals with undernutrition or low inflammatory status with or without undernutrition. In our population, among MCI patients the presence of MetS independently predicted an increased risk of progression to dementia over 3.5 years of follow-up.

This review summarizes available evidence on the beneficial effects of inorganic nitrates and the monounsaturated fatty acid (MUFA) oleic acid, largely contained in Mediterranean diet, on blood pressure and coagulation activity. Inorganic nitrate. Normal vascular function requires NO production from the 1-arginine-NO synthase (NOS) pathway. This process is defective in conditions of local hypoxia, and here nitrite can substitute for 1-arginine-NOS derived NO. In this context, NO generation from the nitrate-nitrite-NO pathway mostly derived from green leafy vegetables appears to be an alternative source for NOS-dependent NO production, ensuring NO bioavailability also in situations when the endogenous 1-arginine/NO synthase pathway is dysfunctional or physiologically reduced in local hypoxic conditions. Olive oil and oleic acid. In addition to effects on lipoprotein metabolism and oxidation, the beneficial effects of oleic acid occur also on coagulation activity, namely on coagulation factor VII (FVII). Normally, a substantial increase of FVII coagulant activity (FVIIc) occurs within 2-3h after a fatty meal and persists for several hours thereafter. When a background diet high in MUFA is consumed, a lower post-prandial increase of FVIIc takes place.