Glucagon-Like Peptide 2 (GLP-2) Stimulates Postprandial Chylomicron Production and Postabsorptive Release of Intestinal Triglyceride Storage Pools via Induction of Nitric Oxide Signaling in Male Hamsters and Mice
| Autor: | Khosrow Adeli, Mahmood Hussain, Joanne Hsieh, Elizabeth J. Lake, Christopher Baker, Jahangir Iqbal, Sarah Farr, Karin Trajcevski, Jennifer Taher |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Male
medicine.medical_specialty Enterocyte medicine.medical_treatment Biology Nitric Oxide Endothelial NOS Nitric oxide Mice chemistry.chemical_compound Endocrinology Cricetinae Internal medicine Chylomicrons Glucagon-Like Peptide 2 medicine Animals Insulin Triglycerides Dyslipidemias Mice Knockout Mesocricetus digestive oral and skin physiology Lipid Metabolism Postprandial Period Glucagon-like peptide-2 Lipids Mice Inbred C57BL Enterocytes NG-Nitroarginine Methyl Ester Postprandial medicine.anatomical_structure chemistry Insulin Resistance Signal Transduction Lipoprotein Chylomicron |
| Zdroj: | Endocrinology. 156:3538-3547 |
| ISSN: | 1945-7170 0013-7227 |
| DOI: | 10.1210/en.2015-1110 |
| Popis: | The intestinal overproduction of apolipoprotein B48 (apoB48)-containing chylomicron particles is a common feature of diabetic dyslipidemia and contributes to cardiovascular risk in insulin resistant states. We previously reported that glucagon-like peptide-2 (GLP-2) is a key endocrine stimulator of enterocyte fat absorption and chylomicron output in the postprandial state. GLP-2's stimulatory effect on chylomicron production in the postabsorptive state has been confirmed in human studies. The mechanism by which GLP-2 regulates chylomicron production is unclear, because its receptor is not expressed on enterocytes. We provide evidence for a key role of nitric oxide (NO) in mediating the stimulatory effects of GLP-2 during the postprandial and postabsorptive periods. Intestinal chylomicron production was assessed in GLP-2-treated hamsters administered the pan-specific NO synthase (NOS) inhibitor L-NG-nitroarginine methyl ester (L-NAME), and in GLP-2-treated endothelial NOS knockout mice. L-NAME blocked GLP-2-stimulated apoB48 secretion and reduced triglycerides (TGs) in the TG-rich lipoprotein (TRL) fraction of the plasma in the postprandial state. Endothelial NOS-deficient mice were resistant to GLP-2 stimulation and secreted fewer large apoB48-particles. When TG storage pools were allowed to accumulate, L-NAME mitigated the GLP-2-mediated increase in TRL-TG, suggesting that NO is required for early mobilization and secretion of stored TG and preformed chylomicrons. Importantly, the NO donor S-nitroso-L-glutathione was able to elicit an increase in TRL-TG in vivo and stimulate chylomicron release in vitro in primary enterocytes. We describe a novel role for GLP-2-mediated NO-signaling as a critical regulator of intestinal lipid handling and a potential contributor to postprandial dyslipidemia. |
| Databáze: | OpenAIRE |
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