FFAR4 Is Involved in Regulation of Neurotensin Release From Neuroendocrine Cells and Male C57BL/6 Mice
| Autor: | Xian Li, Jun Song, Jing Li, B. Mark Evers, Heidi L. Weiss, Todd Weiss, Tianyan Gao, Heather F. Sinner, Stephanie B. Rock, Courtney M. Townsend |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Agonist Male medicine.medical_specialty Docosahexaenoic Acids medicine.drug_class MAP Kinase Signaling System Enteroendocrine Cells Enteroendocrine cell AMP-Activated Protein Kinases Receptors G-Protein-Coupled 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Endocrinology Neuroendocrine Cells Internal medicine Free fatty acid receptor 1 Cell Line Tumor medicine Animals Humans Insulin Phosphorylation Protein kinase A Receptor Neurotensin Research Articles Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Chemistry AMPK 030104 developmental biology Docosahexaenoic acid 030217 neurology & neurosurgery |
| Zdroj: | Endocrinology. 159(8) |
| ISSN: | 1945-7170 |
| Popis: | Neurotensin (NT), a 13 amino-acid peptide, is predominantly released from enteroendocrine cells of the small bowel in response to fat ingestion. Free fatty acid receptors (FFARs) FFAR1 and FFAR4 regulate secretion of gut hormones and insulin. Here, we show that docosahexaenoic acid, a long-chain fatty acid, has the most dramatic effect on NT release. FFAR1 agonists slightly stimulate and FFAR4 agonists dramatically stimulate and amplify NT secretion. Double knockdown of FFAR1 and FFAR4 decreases NT release, whereas overexpression of FFAR4, but not FFAR1, increases NT release. Administration of cpdA, an FFAR4 agonist, but not TAK-875, a selective FFAR1 agonist, increases plasma NT levels and further increases olive oil-stimulated plasma NT levels. Inhibition of MAPK kinase (MEK)/ERK1/2 decreased fatty acid-stimulated NT release but increased AMP-activated protein kinase (AMPK) phosphorylation. In contrast, inhibition of AMPK further increased NT secretion and ERK1/2 phosphorylation mediated by FFAR1 or FFAR4. Our results indicate that FFAR4 plays a more critical role than FFAR1 in mediation of fat-regulated NT release and in inhibitory crosstalk between MEK/ERK1/2 and AMPK in the control of NT release downstream of FFAR1 and FFAR4. |
| Databáze: | OpenAIRE |
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