Non-alcoholic fatty liver disease (NAFLD) is characterized by the aberrant accumulation of triglycerides in hepatocytes in the absence of significant alcohol consumption, viral infection or other specific causes of liver disease. NAFLD has become a burgeoning health problem both worldwide and in China, but its pathogenesis remains poorly understood. Farnesoid X receptor (FXR), a member of the nuclear receptor (NR) superfamily, has been demonstrated to be the primary sensor for endogenous bile acids, and play a crucial role in hepatic triglyceride homeostasis. Deciphering the synergistic contributions of FXR to triglyceride metabolism is critical for discovering therapeutic agents in the treatment of NAFLD and hypertriglyceridemia.

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Chemerin is a newly discovered adipokine which has been found closely associated with obesity, metabolic syndrome (MetS), and inflammatory status. This study will investigate whether serum chemerin levels are associated with coronary artery disease (CAD) independently of other cardiovascular risk factors. This study included a total of 430 subjects (239 with CAD and 191 with non-CAD) who underwent coronary angiography. Anthropometric measurements were performed and chemerin, glucose, lipid profiles, and other biochemical characteristics were measured. The severity of coronary atherosclerosis was estimated by the total number of diseased vessels and Gensini score. Serum chemerin levels were significantly higher in the CAD group than in the non-CAD group (P = 0.011). The odds ratios (95% CI) of CAD across increasing quartiles of serum chemerin were 1.04 (0.61-1.78), 1.08 (0.63-1.83), and 1.87 (1.07-3.24), (P = 0.386, 0.508, and 0.012, respectively). Adjusting for age, sex, and other conventional risk factors for CAD did not appreciably alter the results. Serum chemerin levels were significantly increased with an increasing of number of diseased vessels (P = 0.024). In conditional linear regression models, chemerin levels were positively related to Gensini score even after established cardiovascular risk factors (β = 0.13, P = 0.019). Correlation analysis showed serum chemerin levels were significantly associated with TG levels, TC levels, fasting serum insulin, HOMA-IR and MetS (all P < 0.05). Higher serum chemerin levels were associated with increased risk of CAD and metabolic parameters in Chinese adults. Chemerin may represent a novel link between metabolic signals and atherosclerosis.

Integrins are important for T cell interactions with endothelial cells. Because the integrin αEβ7 is expressed on some circulating gut-homing T cells and as T cell numbers are reduced in the intestinal lamina propria of αE-deficient mice, we evaluated whether αEβ7 mediates binding to intestinal endothelial cells. We found that anti-αEβ7 mAbs partially blocked the binding of cultured intraepithelial T cells to human intestinal microvascular endothelial cells (HIMEC). Furthermore, αEβ7-transfected K562 cells bound more efficiently than vector-transfected K562 cells to HIMEC. Finally, HIMEC bound directly to an αEβ7-Fc fusion protein. These interactions were partially blocked by anti-αEβ7 mAbs, and endothelial cell binding to the αEβ7-Fc was dependent upon the metal ion-dependent adhesion site within the αE A domain. Of note, the HIMEC lacked expression of E-cadherin, the only known αEβ7 counterreceptor as assessed by functional studies, flow cytometry, and RT-PCR. Thus, HIMEC/αEβ7 binding was independent of E-cadherin. In addition, this interaction appeared to be tissue selective, as HIMEC bound to the αEβ7-Fc, whereas microvascular endothelial cells from the skin did not. Finally, there was evidence for an αEβ7 ligand on intestinal endothelial cells in vivo, as αEβ7 expression enhanced lymphocyte binding around vessels in the lamina propria in tissue sections. Thus, we have defined a novel interaction for αEβ7 at a nonepithelial location. These studies suggest a role for αEβ7 in interactions with the intestinal endothelium that may have implications for intestinal T cell homing or functional responses.

This study is to prospectively investigate the association between serum uric acid and the incidence of type 2 diabetes in middle-aged and elderly Chinese. This study consisted of 924 non-diabetic adults aged 40 years or older at baseline. Subjects who received antidiabetic therapies and those who responded positively to the 75-g oral glucose tolerance test according to the 1999 World Health Organization criteria were diagnosed as having type 2 diabetes. Ninety-eight subjects developed type 2 diabetes during the 3.5-year follow-up. The hazard ratio (HR) for incident diabetes was 1.50 [95% confidence interval (CI) 1.18-1.92] for the highest sex-specific quartile of serum uric acid compared with the lowest after controlling for confounders. Participants with hyperuricemia had an HR of 1.95 (95% CI 1.11-3.44) for incident diabetes compared with those without hyperuricemia. Compared with the lowest quartile, the highest quartile had an HR for incident diabetes of 2.45 (95% CI 1.39-4.33) in men and 1.39 (95% CI 1.04-1.84) in women after fully adjustment. Adding serum uric acid to a model of conventional risk factors for diabetes improved the area under the curve for prediction of type 2 diabetes by 5%. Serum uric acid was an independent predictor of incident type 2 diabetes in middle-aged and elderly Chinese.

Ginsenoside Re (Re), a compound derived from Panax ginseng, shows an antidiabetic effect. However, the molecular basis of its action remains unknown. We investigated insulin signaling and the antiinflammatory effect by Re in 3T3-L1 adipocytes and in high-fat diet (HFD) rats to dissect its anti-hyperglycemic mechanism. Glucose uptake was measured in 3T3-L1 cells and glucose infusion rate determined by clamp in HFD rats. The insulin signaling cascade, including insulin receptor (IR) beta-subunit, IR substrate-1, phosphatidylinositol 3-kinase, Akt and Akt substrate of 160 kDa, and glucose transporter-4 translocation are examined. Furthermore, c-Jun NH(2)-terminal kinase (JNK), MAPK, and nuclear factor (NF)-kappaB signaling cascades were also assessed. The results show Re increases glucose uptake in 3T3-L1 cells and glucose infusion rate in HFD rats. The activation of insulin signaling by Re is initiated at IR substrate-1 and further passes on through phosphatidylinositol 3-kinase and downstream signaling cascades. Moreover, Re demonstrates an impressive suppression of JNK and NF-kappaB activation and inhibitor of NF-kappaBalpha degradation. In conclusion, Re reduces insulin resistance in 3T3-L1 adipocytes and HFD rats through inhibition of JNK and NF-kappaB activation.

Significant findings of the studyThe significant associations of the liver enzymes ALT and GGT with metabolic syndrome were independent of insulin resistance measured with HOMA-IR. GGT was superior to ALT for indicating the future development of metabolic syndrome. What this study addsIt confirmed a significant and independent association of liver enzymes with metabolic syndrome, and demonstrated a better relationship between GGT and metabolic syndrome than ALT. Correspondence AbstractBackground: Although associations of the liver enzymes alanine aminotransaminase (ALT) and c-glutamyltransferase (GGT) with metabolic syndrome (MetS) are well recognized, whether they are independent of insulin resistance and which enzyme is more effective are yet to be clarified. Methods: A total of 5404 subjects aged ‡40 years were recruited from two urban communities in Shanghai for cross-sectional analyses. A subgroup of 681 participants without MetS at baseline was included in the longitudinal analyses. Insulin resistance was measured using the homeostasis model assessment of insulin resistance (HOMA-IR), and the modified National Cholesterol Education Program Adult Treatment Panel III criteria were adopted to diagnose MetS. Results: Both GGT and ALT were strongly and positively associated with MetS risks in simple and multivariate analyses. Further adjustment for HOMA-IR and ALT did not change the association of GGT and MetS materially, whereas adjustment for HOMA-IR and GGT substantially attenuated the ALT-MetS association. In longitudinal analyses, risks of developing MetS were increased across GGT quartiles in a dose-dependent manner after extensive adjustments (odds ratios were 1.00, 1.38, 1.62, and 2.29 for GGT, quartile 1 through quartile 4; P for trend = 0.01). In contrast, ALT was no longer associated with MetS development after final adjustment for GGT (P for trend = 0.09). Conclusions: Our study confirmed significant and independent associations of GGT and ALT with MetS in adult Chinese people. Moreover, GGT might be more effective for indicating the future development of MetS.