These findings seem paradoxical given the enhanced inflammation and fibrosis in IDO-KO mice in AbMole Nitisinone response to the HFD. A possible explanation might be that the liver inflammation proceeded earlier in IDO-KO mice, in a similar manner to NAFLD in the clinical setting, where many cases with NAFLD show the disappearance of steatosis during its natural history, while exhibiting severe fibrosis and cirrhosis in the late stages. In order to verify this possibility, time course studies that evaluate the levels of hepatic injury, steatosis, and inflammation caused by HFD in the early phase should be conducted. In addition, a recent study revealed that hepatic fat deposits were broken down to provide energy for fibrogenesis in a CCl4-treated mouse model. Such a mechanism might have also been active in our HFD-fed IDO-KO mice, but again, further experiments will be required to confirm this hypothesis. In conclusion, we herein demonstrated that IDO deficiency worsens hepatic and WAT inflammation in mice fed an HFD. Our findings suggest that regulation of the IDO-mediated immune response might be an interesting strategy for managing steatosis-related hepatic injury. The Western diet has high fructose content, mainly in the form of high fructose corn syrup, which has been proposed to induce hypertension. High fructose diet-fed Sprague-Dawley rats have been widely used as a model of insulin resistance and these rats also develop hypertension. We have shown that fructose-fed SD rats have elevated levels of methylglyoxal, a reactive metabolite of glucose and fructose. Elevated plasma levels of MG have been reported in spontaneously hypertensive rats which correlate with the degree of hypertension, but the cause-effect relationship and the underlying molecular mechanisms are not known. People with diabetes have significantly elevated levels of MG. We have recently reported that chronic MG induces features of type 2 diabetes in SD rats. MG is a major precursor for the formation of advanced glycation end products. MG reduces activity of antioxidant enzymes like glutathione reductase and glutathione peroxidase, leading to increased oxidative stress, which in turn is believed to cause the pathophysiological changes in diabetes, hypertension, and aging. The pathogenesis of hypertension is multifactorial. Some of the factors include an increase in renin angiotensin aldosterone system activity, insulin resistance, renal disease and oxidative stress. The RAAS plays an AbMole LOUREIRIN-B important role in maintaining fluid balance, vascular tone and blood pressure. MG and angiotensin II both lead to an increase in oxidative stress. Ang II stimulates NADPH oxidase by acting through the AT1 receptor and increases 
superoxide, hydrogen peroxide, and peroxynitrite. However, the cause and effect relationship between increased oxidative stress, RAAS activity and increased blood pressure has remained unclear. Here we show that 12 week old male SD rats treated for 16 weeks with a high fructose diet, a precursor of MG, develop a significant increase in blood pressure. The kidney and aorta from fructose treated rats had significantly increased MG levels, and protein and mRNA for renin, Ang II, AT1 and adrenergic a1D receptors, which were attenuated by the MG scavenger metformin. MG treated cultured vascular smooth muscle cells had increased expression of Ang II, AT1 and a1D receptors, which was attenuated by metformin. Although high glucose and high fructose diets have been shown to significantly increase the blood pressure in animals and humans, the molecular mechanisms are not very clear.