Comparative transcriptomic analysis reveals the underlying molecular mechanism in high-fat diet-induced islet...

Area of Science:

• Metabolic research
• Molecular biology
• Endocrinology

Background:

• Obesity is linked to hyperlipidemia, abnormal glucose metabolism, and islet β-cell damage.
• The precise mechanisms driving obesity-induced islet deterioration remain unclear.

Purpose of the Study:

• To investigate the molecular mechanisms underlying high-fat diet (HFD)-induced islet dysfunction in mice.
• To identify differentially expressed genes (DEGs) and pathways affected by HFD in pancreatic islets.

Main Methods:

• C57BL/6 mice were fed a HFD for 2 and 6 months to model obesity.
• RNA sequencing was employed to analyze gene expression changes in isolated islets.
• Gene Ontology (GO) and KEGG pathway analyses were performed on DEGs.

Main Results:

• HFD induced significant changes in gene expression, with 262 DEGs at 2 months and 428 at 6 months.
• Upregulated DEGs were enriched in endoplasmic reticulum stress and pancreatic secretion pathways.
• Downregulated DEGs were associated with neuronal cell bodies and protein digestion/absorption.
• Expression of key islet cell markers (β, α, δ, PP) decreased, while acinar cell markers increased.
• Collagen gene expression was notably downregulated.

Conclusions:

• HFD significantly alters gene expression profiles in pancreatic islets, contributing to dysfunction.
• Endoplasmic reticulum stress and altered secretory pathways are implicated in HFD-induced islet damage.
• The study provides a comprehensive gene expression map for HFD-induced islet dysfunction, aiding further research into obesity-related diabetes mechanisms.