Using apolipoprotein E knock-out (apoE<sup>-/-</sup>) mice on a high fat (HF) diet as an atherosclerotic obesity model, we demonstrated 1) microRNA-155 (miRNA-155, miR-155) is significantly up-regulated in the aortas of apoE<sup>-/-</sup> mice, and miR-155 deficiency in apoE<sup>-/-</sup> mice inhibits atherosclerosis; 2) apoE<sup>-/-</sup>/miR-155<sup>-/-</sup> (double knock-out (DKO)) mice show HF diet-induced obesity, adipocyte hypertrophy, and present with non-alcoholic fatty liver disease; 3) DKO mice demonstrate HF diet-induced elevations of plasma leptin, resistin, fed-state and fasting insulin and increased expression of adipogenic transcription factors but lack glucose intolerance and insulin resistance.
To assess potential gene-drug interactions, mice expressing human apolipoprotein E3 or E4 (APOE3 or APOE4) were fed a Western-type high-fat diet for 12 wk, at which time they developed similarly impaired glucose tolerance.
To investigate whether apolipoprotein E polymorphism modulates the susceptibility to GSD at the population level and to study the possible associations between impaired glucose tolerance, diabetes, and GSD.
Apolipoprotein E (apo E), a component of VLDL, HDL and chylomicron remnants, is inherited at a single genetic locus with 3 common alleles (epsilon 2, epsilon 3 and epsilon 4). epsilon 2 homozygosity is found in 0-2% of healthy populations, but in 75-100% of subjects with type III hyperlipoproteinaemia, in whom an increased prevalence of glucose intolerance has previously been reported.