Cardiac myocyte contractility, calcium dynamics, and morphology in Zucker diabetic fatty female and male rats – lacking data in this model of obesity and diabetes: A review

Diabetes mellitus (DM) represents an increasing global health burden with type 2 diabetes mellitus (T2DM) accounting for most cases. T2DM is associated with microvascular and macrovascular complications including myocardial ischemia and contributes to the development of a distinct form of cardiac dysfunction referred to as diabetic cardiomyopathy (DCM). Importantly, DCM contributes to 50-80% of mortality in patients with diabetes independent of other vascular comorbidities and is characterized by structural and functional alterations of the myocardium. Notably, these outcomes exhibit sex-specific differences in patients with T2DM. Despite this, most preclinical rodent studies fail to incorporate female subjects. This is truly the case of the Zucker diabetic fatty (ZDF) rat model, where the left ventricular contractile and morphological properties have been investigated almost exclusively in males. This review aims to: a) synthesize existing data on myocyte shortening and morphology in ZDF male and female rats; b) identify critical gaps in current knowledge and define priorities for future experiments; and c) emphasize the urgent need for longitudinal studies assessing cardiomyocyte contractility and structural remodeling in both sexes. Cardiac myocyte contractility and calcium dynamics data are entirely lacking in ZDF female rats, while findings in males remain limited and, in some cases, inconsistent. For morphological and ultrastructural alterations in cardiac myocytes information is scarce for both ZDF males and females. Overall, this review highlights the need for comprehensive longitudinal investigations spanning the early and advanced stages of DCM including progression to heart failure in both male and female ZDF rats.