Obesity is a leading risk factor for type 2 diabetes (T2D). Aging is associated with an increase in T2D incidence, which is not totally explained by the much lower prevalence of obesity in the elderly. Low-grade inflammation in adipose tissue (AT) contributes to insulin resistance and T2D. Thus, we determined whether inflammatory responses are up-regulated with age in AT. The results showed that visceral AT from old C57BL mice had significantly higher mRNA expression of the proinflammatory cytokines IL-1β, IL-6, TNF-α, and COX-2 and lower expression of anti-inflammatory PPAR-γ than those of young mice. We further showed that adipocytes (AD) and not stromal vascular cells including macrophages (Mφ) were the cells responsible for this higher inflammatory state of the aged AT, suggesting that the age-associated increase in AT inflammation is distinguished from that seen in obesity, in which Mφ are the main contributors. However, peritoneal Mφ of either age (young or old) produced more TNF-α and IL-6 after incubation in old AD-conditioned medium compared with young AD-conditioned medium. This suggests that in addition to producing more inflammatory cytokines, AD from old mice induce a higher inflammatory response in other cells. Sphingolipid ceramide was higher in old compared with young AD. Reducing ceramide levels or inhibiting NF-κB activation decreased cytokine production, whereas the addition of ceramide increased cytokine production in young AD to a level comparable to that seen in old AD, suggesting that ceramide-induced activation of NF-κB plays a key role in AT inflammation.

A considerable amount of evidence indicates that tumorigenesis is associated with inflammation. Nuclear factor-kappa B (NF-kappa B), a master regulator of infection and inflammation, has been identified as a key modulator in which inflammation could develop into cancer. Dietary polyphenols have been shown to have anti-inflammatory and anticancer activity partially through inhibition of NF-kappa B activation. This review summarizes the effect of polyphenols on inflammation and cancer; avenanthramides, a unique polyphenol from oats, are especially focused.

A potential mechanism by which green tea may prevent cancer development is through the inhibition of angiogenesis. We have shown previously that the green tea catechin, epigallocatechin gallate (EGCG), inhibits endothelial cell tube formation through the inhibition of vascular endothelial growth factor (VEGF)‐induced Akt activation and vascular endothelial (VE)‐cadherin phosphorylation. Furthermore, EGCG can suppress oxidant‐induced production of the proangiogenic cytokine interleukin (IL)‐8. To further elucidate the antiangiogenic mechanisms of EGCG, we investigated its regulation of other molecular processes in VEGF‐induced signaling in human umbilical vein endothelial cells (HUVECs). We show that EGCG at physiological doses (0.5–10 μM) markedly inhibits the formation of a vascular endothelial growth factor receptor 2 complex formed upon the binding of its ligand VEGF. This disruption results in a significant and dose‐dependent decrease in PI3‐kinase activity. Electrophoretic mobility shift assay revealed that EGCG decreased the PI3 kinase‐dependent activation and DNA‐binding ability of NF‐κB, likely acting through decreasing phosphorylation and degradation of IκB. VEGF‐induced IL‐8 production at the mRNA (real time RT‐PCR) and protein levels (ELISA) are also suppressed with EGCG. These results suggest a novel mechanism for green tea's anticancer effects where EGCG can abrogate VEGF signaling by interfering with the formation of a receptor complex, resulting in attenuated mitogenic and angiogenic signaling.

Accumulation of damaged proteins is causally related to many age‐related diseases. The ubiquitin‐proteasome pathway (UPP) plays a role in selective degradation of damaged proteins, whereas molecular chaperones, such as heat shock proteins, are involved in refolding denatured proteins. This work demonstrates for the first time that the UPP and molecular chaperones work in a competitive manner and that the fates of denatured proteins are determined by the relative activities of the UPP and molecular chaperones. Enhanced UPP activity suppresses the refolding of denatured proteins whereas elevated chaperone activity inhibits the degradation of denatured proteins. CHIP, a co‐chaperone with E3 activity, plays a pivotal role in determining the fates of the damaged proteins. The delicate balance between UPP‐mediated degradation and refolding of denatured proteins is governed by relative levels of CHIP and other molecular chaperones. Isopeptidases, the enzymes that reverse the actions of CHIP, also play an important role in determining the fate of denatured proteins.