Comparison of human and rodent cell models to study myocardial lipid-induced insulin resistance

Isolated or cultured cells have proven to be valuable model systems to investigate cellular (patho)biology and for screening of the efficacy of drugs or their possible side-effects. Pluripotent stem cells (PSC) can be readily obtained from healthy individuals as well as from diseased patients, and protocols have been developed to differentiate these cells into cardiomyocytes. Hence, these cellular models are moving center stage for a broader application. In this review, we focus on comparing mouse HL-1 cardiomyocytes, isolated adult rat cardiomyocytes, human embryonic stem cell-derived cardiomyocytes (hESC-CMs) and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) for the study of metabolic aspects of cardiac functioning in health and disease. Various studies have reported that these cellular models are suitable for assessing substrate uptake and utilization, in that each display an adequate and similar response to physiological triggers, in particular the presence of insulin. Likewise, disease conditions, such as excess lipid supply, similarly affect each of these rodent and human cardiomyocyte models. It is concluded that PSC-CMs obtained from patients with cardiogenetic abnormalities are promising models to evaluate the functional consequence of gene variants with unknown significance.