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Ceramides Increase Fatty Acid Utilization in Intestinal Progenitors to Enhance Stemness and Increase Tumor Risk.
Ying Li1, Bhagirath Chaurasia2, M Mahidur Rahman3
1Department of Nutrition and Integrative Physiology and the Diabetes and Metabolism Research Center, University of Utah, Salt Lake City, Utah.
Gastroenterology
|August 4, 2023
Summary
High nutrient intake increases cancer risk by altering stem cell behavior. Ceramides, signaling molecules for nutritional excess, promote intestinal cell proliferation and lipid metabolism, linking diet to cancer development.
Area of Science:
- Gastroenterology
- Oncology
- Molecular Biology
Background:
- Obesity is linked to alimentary tract cancers like esophageal, colorectal, and gastric cardia cancers.
- Excessive nutrient delivery disrupts intestinal stem cell balance, increasing cancer risk.
- Ceramides, sphingolipids indicating nutritional excess, are investigated for their role in stem cell behavior and cancer risk.
Purpose of the Study:
- To investigate if ceramides alter stem cell behavior and influence cancer risk.
- To understand the role of sphingolipids in intestinal stem cell homeostasis and cancer development.
Main Methods:
- Profiling sphingolipids and related enzymes in human tumors and adenomas.
- Manipulating sphingolipid synthesis enzymes (e.g., serine palmitoyltransferase (SPT)) in mouse intestinal progenitors, organoids, and Drosophila.
- Assessing the impact of sphingolipids on stem cell proliferation and metabolism.
Main Results:
- Serine palmitoyltransferase (SPT) and other sphingolipid biosynthesis enzymes are upregulated in human intestinal adenomas.
- SPT diverts nutrients into ceramide production, a critical regulator of intestinal stem cell homeostasis.
- Ceramides act as pro-stemness signals, enhancing lipid utilization and intestinal progenitor proliferation.
Conclusions:
- Ceramides are key mediators linking dietary macronutrients to epithelial regeneration and cancer risk.
- Understanding ceramide-driven pathways offers insights into obesity-related gastrointestinal cancers.
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