Influence of gender and time diet exposure on endocrine pancreas remodeling in response to high fat diet-induced metabolic disturbances in mice

Abstract

In this study, we investigated a possible sexual dimorphism regarding metabolic response and structural and functional adaptations of the endocrine pancreas after exposure to a high-fat diet (HFd). On chow diet, male and female C57BL/6/JUnib mice showed similar metabolic and morphometric parameters, except that female islets displayed a relatively lower β-cell:non-β-cell ratio. After 30 days on HFd, both male and female mice showed increased weight gain, however only the males displayed glucose intolerance associated with high postprandial glycemia when compared to their controls. After 60 days on HFd, both genders became obese, hyperglycemic, hyperinsulinemic, insulin resistant and glucose intolerant, although the metabolic changes were more pronounced in males, while females displayed greater weight gain. In both genders, insulin resistance induced by HFd feeding was compensated by expansion of β-cell mass without changes in islet cytoarchitecture. Interestingly, we found a strong correlation between the degree of β-cell expansion and the levels of hyperglycemia in the fed state: male mice fed a 60d-HFd, showing higher glycemic levels also displayed a greater β-cell mass increase in comparison with female mice. Additionally, sexual dimorphism was also observed regarding the source of β-cell mass expansion following 60d-HFd: while in males, both hypertrophy and hyperplasia (revealed by morphometry and Ki67 immunoreaction) of β-cells were observed, female islets displayed only a significant increase in β-cell size. In conclusion, this study describes gender differences in metabolic response to high fat diet, paralleled by distinct compensatory morphometric changes in pancreatic islets.