Functional peroxisomes are required for β-cell integrity in mice

Molecular Metabolism
Ritesh Kumar BabootaMyriam Baes

Abstract

Peroxisomes play a crucial role in lipid and reactive oxygen species metabolism, but their importance for pancreatic β-cell functioning is presently unknown. To examine the contribution of peroxisomal metabolism to β-cell homeostasis in mice, we inactivated PEX5, the import receptor for peroxisomal matrix proteins, in an inducible and β-cell restricted manner (Rip-Pex5-/- mice). 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. 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. Consiste...Continue Reading

Citations

Mar 27, 2020·Frontiers in Cellular Neuroscience·Ndidi-Ese UzorAndrey S Tsvetkov
Jan 10, 2021·Journal of Diabetes and Its Complications·Helen R BlairMark Walker
Oct 22, 2019·Journal of Molecular Biology·Leticia P Roma, Jean-Christophe Jonas
Dec 10, 2019·Biochimica Et Biophysica Acta. Molecular Cell Research·Lucie OberhauserPierre Maechler
Apr 4, 2021·Antioxidants·Štěpánka BenákováLydie Plecitá-Hlavatá
May 22, 2021·Diabetes·Gemma L PearsonScott A Soleimanpour
Sep 3, 2021·Oxidative Medicine and Cellular Longevity·Hongbo GuanXiaomei Liu
Jan 26, 2022·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jonathan MuriManfred Kopf

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Methods Mentioned

BETA
ELISA
transmission electron microscopy
RNA-seq
RNAseq
PCA
transgenic

Software Mentioned

GSEA
R
GraphPad Prism
Image Lab
package EdgeR
Kallisto
Limma

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