In strictly identical experimental conditions, HFD-fed C57BL/6J and BALB/c developed concordant pathophysiological features (hypercholesterolemia, enhanced insulin secretion, increased adiposity), as well as contrasting phenotypic adaptations to HFD in relation to the regulation of glucose tolerance, body weight and liver histology and triglycerides content. This evidence concerns the gene INS and familial hypercholesterolemia.