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Islet Proteome Remodeling and Proteostasis Disruption in HFSC-Fed Mice
Vijayalakshmi Gangadhara1, Yalpi Karthik2, Ravichandran Manisekaran3
1Father George Albuquerque Pai Cell and Molecular Biology Laboratory, Department of Biotechnology, School of Life Sciences, St Aloysius (Deemed to be University), Mangaluru 575003, Karnataka, India.
High-fat, simple-carbohydrate diets cause pancreatic stress and metabolic changes. Proteomic analysis revealed altered protein expression in islets, indicating increased biosynthesis and ER stress, alongside metabolic remodeling, offering insights into early islet dysfunction.
Area of Science:
- Metabolomics
- Proteomics
- Cellular Biology
Background:
- Chronic overnutrition is linked to metabolic syndrome and pancreatic stress.
- Early molecular changes in pancreatic islets under such conditions are not fully understood.
- High-fat, simple-carbohydrate (HFSC) diets induce pancreatic steatosis, acinar atrophy, and islet hypertrophy.
Purpose of the Study:
- To investigate the proteomic alterations in pancreatic islets of mice fed an HFSC diet.
- To identify molecular responses underlying HFSC-induced pancreatic remodeling.
- To understand early islet dysfunction in diet-induced metabolic syndrome.
Main Methods:
- Proteomic profiling of collagenase-isolated pancreatic islets from male C57BL/6J mice using label-free ESI-nanoLC-MS/MS.
- Analysis of 386 identified proteins using stringent filtering and statistical criteria (≥2 peptides, ≥1 unique peptide, fold change ≥ 1.5, FDR-adjusted q-value ≤ 0.05).
- Functional enrichment analysis of differentially expressed proteins.
Main Results:
- 30 differentially expressed proteins were identified (19 upregulated, 11 downregulated) in HFSC-fed mice islets.
- Upregulated pathways included cytoplasmic translation and ER protein folding, suggesting increased biosynthesis and proteostasis.
- Downregulated proteins were enriched in metabolic pathways, and key stress-responsive proteins were reduced, indicating ER stress.
Conclusions:
- HFSC diet induces significant proteomic adaptations in pancreatic islets.
- These adaptations involve increased biosynthetic activity, altered metabolic pathways, and ER stress.
- The findings provide proteomic evidence for molecular events contributing to early islet dysfunction in metabolic syndrome.
