Conclusions
Our data indicate that normal peroxisome metabolism in β-cells is crucial to preserve their structure and function.
Methods
After tamoxifen-induced recombination of the Pex5 gene at the age of 6 weeks, mice were fed either normal chow or a high-fat diet for 12 weeks and were subsequently phenotyped.
Results
Increased levels of very long chain fatty acids and reduced levels of plasmalogens in islets confirmed impairment of peroxisomal fatty acid oxidation and ether lipid synthesis, respectively. The Rip-Pex5-/- mice fed on either diet exhibited glucose intolerance associated with impaired insulin secretion. Ultrastructural and biochemical analysis revealed a decrease in the density of mature insulin granules and total pancreatic insulin content, which was further accompanied by mitochondrial disruptions, reduced complex I activity and massive vacuole overload in β-cells. RNAseq analysis suggested that cell death pathways were affected in islets from HFD-fed Rip-Pex5-/- mice. Consistent with this change we observed increased β-cell apoptosis in islets and a decrease in β-cell mass. Conclusions: Our data indicate that normal peroxisome metabolism in β-cells is crucial to preserve their structure and function.