Integrated transcriptomic analyses identify altered nerve triglycerides in mouse models of prediabetes and type 2 diabetes

We employed high-fat diet (HFD)-induced prediabetes and HFD/streptozotocin (STZ)-induced type 2 diabetes mouse models that develop PN, which we compared to control mice maintained on standard diet (SD) and to HFD and HFD/STZ mice that were subject to SD dietary reversal (DR) half-way through the study. We performed gene expression profiling on sciatic nerves from SD, HFD, HFD-STZ, HFD-DR, and HFD-STZ-DR animal cohorts. Nerve transcriptomic profiles were integrated using complex correlation analyses, and biological meaning was inferred from known lipid-gene interactions in the literature mRNA profiles of sciatic nerve (SCN) tissue was isolated from 16-week and 24-week old C57BL/6J mice that were under . Our prediabetic model consisted of BL/6J mice fed a HFD (60% kcal fat) from 5 weeks of age. Our T2D diabetic model consisted of 12-week old HFD mice injected with low dose streptozotocin (STZ; 75mg/kg followed by a 50mg/kg dose 3 days later (i.p. injection)). At 16 weeks, subgroups of HFD and HFD-STZ mice were switched to a control diet (13% kcal fat) for 8 weeks to mimic dietary reversal. RNA-seq of SCN was performed on SCN tissue at the 16 week and 24 week timepoints.