ArticlePloS one2017
Long chain saturated and unsaturated fatty acids exert opposing effects on viability and function of GLP-1-producing cells: Mechanisms of lipotoxicity.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- The Role of Fatty Acids in Ceramide Pathways and Their Influence on Hypothalamic Regulation of Energy Balance: A Systematic Review.International journal of molecular sciences · 2021Pooled it
- AA in Obesity and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) Nonalcoholic Fatty Liver Disease (NAFLD).Reviews of physiology, biochemistry and pharmacology · 2027Review
- Influence of Extraction Methods on the Physicochemical and Biological Properties of Amazonian Beetle Larva Oil (ACS omega · 2026Article
- GLP-1 Receptor Agonists at the Crossroads of Circadian Biology, Sleep, and Metabolic Disease.International journal of molecular sciences · 2026Review
- Therapeutic Potential of Infrared and Related Light Therapies in Metabolic Diseases.International journal of molecular sciences · 2025Review
- A disturbed communication between hypothalamic-pituitary-ovary axis and gut microbiota in female infertility: is diet to blame?Journal of translational medicine · 2025Review
- The Impact of the Mediterranean Diet on Telomere Biology: Implications for Disease Management-A Narrative Review.Nutrients · 2024Review
- Tripterygium glycosides improve abnormal lipid deposition in nephrotic syndrome rat models.Renal failure · 2023Article
- Regulation of semen quality by fatty acids in diets, extender, and semen.Frontiers in veterinary science · 2023Review
- Circadian secretion rhythm of GLP-1 and its influencing factors.Frontiers in endocrinology · 2022Review
- Mediterranean Diet as an Antioxidant: The Impact on Metabolic Health and Overall Wellbeing.Nutrients · 2021Review
- G protein-coupled receptors as potential targets for nonalcoholic fatty liver disease treatment.World journal of gastroenterology · 2021Review
- Restoration of GLP-1 secretion by Berberine is associated with protection of colon enterocytes from mitochondrial overheating in diet-induced obese mice.Nutrition & diabetes · 2018Article
- Palmitate- and C6 ceramide-inducedNutrition & metabolism · 2018Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
aimFatty acids acutely stimulate GLP-1 secretion from L-cells in vivo. However, a high fat diet has been shown to reduce the density of L-cells in the mouse intestine and a positive correlation has been indicated between L-cell number and GLP-1 secretion. Thus, the mechanism of fatty acid-stimulated GLP-1 secretion, potential effects of long-term exposure to elevated levels of different fatty acid species, and underlying mechanisms are not fully understood. In the present study, we sought to determine how long-term exposure to saturated (16:0) and unsaturated (18:1) fatty acids, by direct effects on GLP-1-producing cells, alter function and viability, and the underlying mechanisms.
methodsGLP-1-secreting GLUTag cells were cultured in the presence/absence of saturated (16:0) and unsaturated (18:1) fatty acids (0.125 mM for 48 h, followed by analyses of viability and apoptosis, as well as involvement of fatty acid oxidation, free fatty acid receptors (FFAR1) and ceramide synthesis. In addition, effects on the expression of proglucagon, prohormone convertase 1/3 (PC1/3), free fatty acid receptors (FFAR1, FFAR3), sodium glucose co-transporter (SGLT) and subsequent secretory response were determined.
resultsSaturated (16:0) and unsaturated (18:1) fatty acids exerted opposing effects on the induction of apoptosis (1.4-fold increase in DNA fragmentation by palmitate and a 0.5-fold reduction by oleate; p<0.01). Palmitate-induced apoptosis was associated with increased ceramide content and co-incubation with Fumonisin B1 abolished this lipo apoptosis. Oleate, on the other hand, reduced ceramide content, and-unlike palmitate-upregulated FFAR1 and FFAR3, evoking a 2-fold increase in FFAR1-mediated GLP-1 secretion following acute exposure to 0.125 mmol/L palmitate; (p<0.05). CONCLUSION/
interpretationSaturated (16:0), but not unsaturated (18:1), fatty acids induce ceramide-mediated apoptosis of GLP-1-producing cells. Further, unsaturated fatty acids confer lipoprotection, enhancing viability and function of GLP-1-secreting cells. These data provide potential mechanistic insight contributing to reduced L-cell mass following a high fat diet and differential effects of saturated and unsaturated fatty acids on GLP-1 secretion in vivo.
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