Regulation of cytoplasmic lipid droplet mobilization in intestinal enterocytes
| dc.contributor.advisor | Xiao, changting | |
| dc.contributor.committeeMember | Campanucci, Veronica | |
| dc.contributor.committeeMember | Widenmaier, Scott | |
| dc.contributor.committeeMember | Fisher, Thomas | |
| dc.creator | Ghanem, Murooj | |
| dc.date.accessioned | 2024-01-29T20:30:09Z | |
| dc.date.available | 2024-01-29T20:30:09Z | |
| dc.date.copyright | 2023 | |
| dc.date.created | 2023-12 | |
| dc.date.issued | 2024-01-29 | |
| dc.date.submitted | December 2023 | |
| dc.date.updated | 2024-01-29T20:30:09Z | |
| dc.description.abstract | Objectives: In postabsorptive state, lipids in intestinal enterocytes in the form of cytoplasmic lipid droplets (CLDs) are mobilized towards chylomicron (CM) synthesis and secretion. The regulatory mechanism of CLD mobilization in enterocytes remains unclear. We hypothesized that CLD mobilization in enterocytes is regulated on a molecular level. The objective of this research is to analyze the lipid output and tissue lipids along with proteomes of CLDs and ER isolated from enterocytes harvested from the small intestine of rats following a cue known to mobilize CLDs. Method: Mesenteric lymph duct and duodenum of male Sprague-Dawley rats were surgically cannulated. Rats received a bolus intraduodenal infusion of intralipid. 5 hours later, rats received the treatment (intraduodenal glucose or saline as control). Lymph fluid was collected for 15 minutes to measure lymph flow rates, and TG and apolipoprotein B48 (apoB48) outputs. At the end of lymph collection, the duodenum and jejunum were harvested. Neutral lipids in the jejunum were visualized with oil red O staining. Enterocytes were isolated, from which CLDs and ER fractions were further isolated. Using proteomics, the total proteins found in the CLD and ER fractions were analyzed to compare the proteins present in the CLD mobilization state (glucose treated) and in the control. Results: Administration of glucose into the duodenum led to an increase in lymph flow rate as compared to the control. Glucose also led to increased TG output as compared to the control. Lymph apoB48 output was higher in glucose than in control. Glucose administration reduced neutral lipids in jejunal tissues compared with control. Proteomics analysis revealed differential abundance in the proteomes in both the CLD and ER fractions between glucose and control. Top ranked proteins suggest treatment-dependent changes in various biological processes and identify a range of candidate proteins that have vesicular transport, hydrolase activity, and lipid metabolism functions. Conclusion: These results show that glucose in the duodenum stimulates the release of stored neutral lipids towards CM synthesis and secretion. CLD active mobilization is accompanied by differential presence of proteins on CLDs and ER that are likely molecular regulators of CLD mobilization. | |
| dc.format.mimetype | application/pdf | |
| dc.identifier.uri | https://hdl.handle.net/10388/15468 | |
| dc.language.iso | en | |
| dc.subject | cytoplasmic lipid droplets, chylomicron, enterocytes | |
| dc.title | Regulation of cytoplasmic lipid droplet mobilization in intestinal enterocytes | |
| dc.type | Thesis | |
| dc.type.material | text | |
| thesis.degree.department | Anatomy, Physiology, and Pharmacology | |
| thesis.degree.discipline | Anatomy, Physiology, and Pharmacology | |
| thesis.degree.grantor | University of Saskatchewan | |
| thesis.degree.level | Masters | |
| thesis.degree.name | Master of Science (M.Sc.) |