👤 Mora Murri

The mechanisms involved in the progression to overt diabetes in pre-obese subjects remain unclear. Therefore, a nontargeted evaluation of differences in the protein abundance of visceral adipose tissue (VAT) obtained from pre-obese diabetic subjects and pre-obese subjects showing normal glucose tolerance may provide novel insights on the molecular processes involved in the progression to overt diabetes in pre-obesity. Diabetic patients showed increased VAT abundance of glutathione S-transferase Mu 2, peroxiredoxin-2, antithrombin-III, apolipoprotein A-IV, Ig κ chain C region, mitochondrial aldehyde dehydrogenase and actin, and decreased abundance of annexin-A1, retinaldehyde dehydrogenase-1, and vinculin, compared with their non-diabetic counterparts. These proteins are involved in cytoskeleton function and structure, oxidative stress, inflammation and retinoid metabolism. The presence of diabetes influences the VAT abundance of several proteins. Hence, the proteins identified here could be considered candidate molecules in future studies addressing the role that VAT dysfunction plays in the development of type 2 diabetes. Show less

Apolipoprotein A5 is a key gene controlling VLDL synthesis and hydrolysis and is the target of the main pharmacological agent to lower triglycerides (fibrates). We hypothesised that variability in the promoter of the APOA5 gene may affect the individual response to fibrate therapy, in both the fasting and postprandial states. We selected 50 subjects with the metabolic syndrome who also had important increase in fasting triglycerides. A subgroup of 36 patients underwent lipid-lowering treatment with 160 mg/day of fenofibrate (Secalip) for 3 months. The participants underwent a 60 g fat overload with a commercial preparation, after which we assessed the influence of the -1131T>C APOA5 SNP on the postprandial response. Compared with non-carriers, the C allele carriers had significantly higher triglyceride levels at baseline (54.87%), and at 3h (61.08%) and 4h (68.35%). Other lipid parameters were not affected by the APOA5 genotype. Our results indicate that carriers of the -1131C allele had a better response to fenofibrate treatment (reduction in triglyceride levels of 40.33% at baseline, P=0.018; and postprandially, 37.64% at 3h, P=0.028 and 42.58% at 4h after the high-fat meal, P=0.018) than wild-type subjects (30.91% decrease at baseline, P<0.001; and 26.61% at 3h P=0.005 and 22.95% at 4h P=0.033 after the high-fat meal). Thus, the treatment for patients with the metabolic syndrome and elevated plasma triglyceride levels may vary according to whether they carry the APOA5 -1131T>C polymorphism. Show less