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

Author(s)

Oliveira, R. B. ^[1] ; Maschio, D. A. ^[1] ; Carvalho, C. P. F. ^[2] ; Collares-Buzato, C. B. ^[1]

Affiliation

^[1] Univ Campinas UNICAMP, Dept Biochem & Tissue Biol, Inst Biol, BR-13083970 Campinas, SP - Brazil

^[2] Univ Fed Sao Paulo, Dept Biosci, Santos, SP - Brazil

• Document type: Journal article
• Source: ANNALS OF ANATOMY-ANATOMISCHER ANZEIGER; v. 200, p. 88-97, 2015.
• Web of Science Citations: 18

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 beta-cell:non-beta-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 beta-cell mass without changes in islet cytoarchitecture. Interestingly, we found a strong correlation between the degree of beta-cell expansion and the levels of hyperglycemia in the fed state: male mice fed a 60 d-HFd, showing higher glycemic levels also displayed a greater beta-cell mass increase in comparison with female mice. Additionally, sexual dimorphism was also observed regarding the source of beta-cell mass expansion following 60 d-HFd: while in males, both hypertrophy and hyperplasia (revealed by morphometry and Ki67 immunoreaction) of beta-cells were observed, female islets displayed only a significant increase in beta-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. (C) 2015 Elsevier GmbH. All rights reserved. (AU)

• FAPESP's process: 10/50789-1 - Role of cell-cell contacts mediated by intercellular junctions and their constitutive proteins in the functional maturation and dysfunction of pancreatic beta cells
• Grantee: Carla Beatriz Collares Buzato
• Support Opportunities: Regular Research Grants
• FAPESP's process: 09/52824-1 - Pancreatic B-cell proliferation and differentiation in animal models of insulin resistance: involvement of the Wnt/beta-catenina signaling pathway
• Grantee: Carla Beatriz Collares Buzato
• Support Opportunities: Regular Research Grants