Abstract
Deposition of heart fat, termed epicardial adipose tissue (EAT), is strongly linked to cardio- metabolic disease. Previous studies have shown that EAT deposition in females aged 60 years and over is greater compared to males of the same body-mass index (BMI) and age. There is a poor understanding of whether the sex differences in EAT deposition is paralleled by sex differences in EAT adipocyte morphology and EAT lipid droplet size. This study aims to test the hypothesis that sex differences exist in EAT adipocyte and lipid droplet size, whereby female EAT adipocytes and lipid droplets are larger in size and greater in number compared to males.
EAT samples were collected from gender-typical biological female (n =14) cardiac surgery patients and age- (68.7 years vs. 68.9 years, p > 0.05) matched biological men (n =14). Importantly, the EAT thickness in these female patients was significantly greater than the male patients (30% thicker, p = 0.004). EAT sections were stained using haematoxylin and eosin to determine EAT adipocyte size. In separate EAT sections of the same patients, immunofluorescent staining using perilipin-1 was used to determine the size of lipid droplets within EAT adipocytes, and DAPI staining was used to measure the number of nuclei within EAT. Female EAT adipocytes (p = 0.04) and EAT lipid droplets (p = 0.03) were significantly smaller than males, but only when patients with type 2 diabetes were excluded. Whether used as either a categorical or continuous variable, BMI was not associated with EAT adipocyte or lipid droplet size in females or males. Interestingly, EAT adipocyte and lipid droplet size showed robust correlations in the total cohort (r2 = 0.5, p < 0.0001) and males (r2 = 0.6, p = 0.0006), but not females. Finally, upon removal of participants with type 2 diabetes, females had a significantly higher adipocyte nuclei count compared to males (p = 0.02).
This research shows for the first time that sex differences exist in EAT adipocyte morphology, and type 2 diabetes might influence this relationship as a confounder. Similarly, sex differences in EAT adipocyte morphology are paralleled by differences in the fat storage site of adipocytes and potentially by infiltration of other non-adipocyte cell types into EAT. When combined with the greater overall EAT thickness, the smaller EAT adipocytes and lipid droplets in females might suggest that hyperplasia drives EAT expansion in females. These results provide insight into how biological sex determines EAT adipocyte morphology and provides the basis for future research into how these sex differences influence the association of EAT with cardio-metabolic disease.