A novel mouse model of nonalcoholic steatohepatitis with significant insulin resistance.

Currently available models insufficiently reflect the pathogenic alternation of nonalcoholic steatohepatitis\NASH), such as insulin resistance. The present study aimed to characterize a novel NASH model caused by feeding the diet containing conjugated linoleic acid (CLA). In this study, mice were fed a control diet or the diet containing 0.5% CLA for 8 weeks. The insulin tolerance test (ITT) and homeostasis model assessment of insulin resistance (HOMA-IR) were used to determine the extent of insulin resistance. Liver lipotoxicity and inflammation were assessed by endoplasmic reticulum (ER) stress, autolipophagy, recruitment of Kupffer cells and hepatic stellate cell (HSC) activation. We found that liver weight was markedly increased, and histopathological examination showed marked macrosteatosis with focal hepatocellular death through apoptosis, and mild pericellular fibrosis with Kupffer cell recruitment and HSC activation, as well as light chain IIIß-positive cells and enhanced ER stress in mice fed the CLA-containing diet. Enhanced synthesis and reduced ß-oxidation of fatty acids resulted in their accumulation and lipotoxicity in hepatocytes. A biophotonic technology revealed lipid droplet accumulation in the liver from mice fed the CLA-containing diet, and Raman spectroscopic analysis indicated that these lipid droplets predominantly contained saturated fatty acids. Elevated fasting insulin levels, abnormal ITT and HOMA-IR confirmed the marked insulin resistance in these mice. Decreased phosphorylation of the insulin-signaling molecule Akt was partially responsible for the significant insulin resistance. In conclusion, Mice fed the diet containing CLA-developed steatohepatitis with marked insulin resistance, which is similar to the characteristics observed in NASH patients. The further characterization of this model would be particularly useful for revealing the critical role of insulin resistance in NASH development in conditions such as metabolic syndrome, diabetes and obesity.

Sweet bing cherries lower circulating concentrations of markers for chronic inflammatory diseases in healthy humans.

A limited number of studies have demonstrated that some modulators of inflammation can be altered by the consumption of sweet cherries. We have taken a proteomics approach to determine the effects of dietary cherries on targeted gene expression. The purpose was then to determine changes caused by cherry consumption in the plasma concentrations of multiple biomarkers for several chronic inflammatory diseases in healthy humans with modestly elevated C-reactive protein (CRP; range, 1-14 mg/L; mean, 3.5 mg/L; normal, <1.0 mg/L). Eighteen men and women (45-61 y) supplemented their diets with Bing sweet cherries (280 g/d) for 28 d. Fasting blood samples were taken before the start of consuming the cherries (study d 7), 28 d after the initiation of cherry supplementation (d 35), and 28 d after the discontinuation (d 63). Of the 89 biomarkers assessed, cherry consumption for 28 d altered concentrations of 9, did not change those of 67, and the other 13 were below the detection limits. Cherry consumption decreased (P < 0.05) plasma concentrations of extracellular newly identified ligand for the receptor for advanced glycation end products (29.0%), CRP (20.1%), ferritin (20.3%), plasminogen activator inhibitor-1 (19.9%), endothelin-1 (13.7%), epidermal growth factor (13.2%), and IL-18 (8.1%) and increased that of IL-1 receptor antagonist (27.9%) compared with corresponding values on study d 7. The ferritin concentration continued to decrease between d 35 and 63 and it was significantly lower on d 63 than on d 7. Because the participants in this study were healthy, no clinical pathology end points were measured. However, results from the present study demonstrate that cherry consumption selectively reduced several biomarkers associated with inflammatory diseases.