{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/124651"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/124651","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Lipid metabolism and small intestine homeostasis","abstract":"Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2026-05-01","abstract_html":"Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2026-05-01","abstract_has_math":false,"creators":["Shi, Ruicheng"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"VMS - Comparative Biosciences","degree_department":null,"school":null,"contributors":["Wang, Bo","Nelson, Erik R","Spinella, Michael J","Mei, Wenyan"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2024,"date_issued":"2024-05","date_published":"2024-05","updated_at":"2026-07-22T22:25:02Z","subjects":["Small Intestine","Lipid Metabolism","Obesity","Sec16b","Chylomicron","Stem Cell","Regeneration"],"languages":["en","eng"],"rights":["Copyright 2024 Ruicheng Shi"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/2142/124651","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Wang, Bo","Nelson, Erik R","Spinella, Michael J","Mei, Wenyan"]},{"key":"dc:creator","label":"Author","values":["Shi, Ruicheng"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2024-05","2024-04-15"]},{"key":"dc:type","label":"Dc Type","values":["text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["VMS - Comparative Biosciences"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Small Intestine","Lipid Metabolism","Obesity","Sec16b","Chylomicron","Stem Cell","Regeneration"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en","eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 2024 Ruicheng Shi"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://hdl.handle.net/2142/124651"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2026-05-01","The student, Ruicheng Shi, accepted the attached license on 2024-04-10 at 15:01.","The student, Ruicheng Shi, submitted this Dissertation for approval on 2024-04-10 at 15:53.","This Dissertation was approved for publication on 2024-04-15 at 16:50.","DSpace SAF Submission Ingestion Package generated from Vireo submission #20349 on 2024-09-16 at 00:49:11","Enterocytes play a major role in lipid absorption. In the enterocytes, dietary lipids are packed into chylomicrons and ultimately secreted into the circulation. The dysregulation of chylomicron biogenesis has been linked to various metabolic disorders including obesity. However, the regulation and production of chylomicron is not yet fully understood. Our first study demonstrated that SEC16B, an endoplasmic reticulum (ER) scaffold protein, regulates chylomicron and obesity in vivo. The single-nucleotide polymorphisms (SNPs) in the SEC16B gene have been identified by numerous genome-wide association studies (GWAS) to be associated with obesity and higher body mass index (BMI). Our study showed that Sec16b deletion in mouse intestines, especially in females, alleviates high-fat diet-induced obesity and improves glucose metabolism. We also demonstrated that mice with dysfunctional Sec16b have significantly reduced post-prandial serum triglyceride (TG) contents when orally administered with lipid bolus. Mechanistically, loss of Sec16b impairs apoB-48 lipidation and hinders pre-chylomicron export from the ER. In summary, our first study identified Sec16b as an essential regulator for chylomicron biogenesis and obesity. Enterocytes work in hazardous environments and need constant replenishment. Our second study focuses on the regulation of intestinal epithelium renewal. Intestinal stem cells (ISCs) in crypts drive enterocyte renewal and are regulated by several factors including lipids. A previous study showed increased cholesterol biosynthesis and cellular cholesterol levels stimulate crypt proliferation. However, whether circulating cholesterol will affect ISC proliferation is still unknown. Our results showed that deletion of low-density lipoprotein receptor (LDLR) moderately enhances ISC proliferation. Treating crypts with LDL ex vivo impairs initial organoid formation but enhances the stemness of the surviving organoids. Unexpectedly, Ldlr-/- and wild-type (WT) organoids reacted similarly to LDL treatment, suggesting that the effect of LDL is not dependent on LDLR. Moreover, loss of Ldlr-/- hinders small intestine regeneration. Taken together, these findings underline the complex role of circulating LDL-cholesterol in ISC homeostasis and self-renewal."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Lipid metabolism and small intestine homeostasis"]}]}],"canonical_facts":{"dc:contributor":["Wang, Bo","Nelson, Erik R","Spinella, Michael J","Mei, Wenyan"],"dc:creator":["Shi, Ruicheng"],"dc:date":["2024-05","2024-04-15"],"dc:description":["Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2026-05-01","The student, Ruicheng Shi, accepted the attached license on 2024-04-10 at 15:01.","The student, Ruicheng Shi, submitted this Dissertation for approval on 2024-04-10 at 15:53.","This Dissertation was approved for publication on 2024-04-15 at 16:50.","DSpace SAF Submission Ingestion Package generated from Vireo submission #20349 on 2024-09-16 at 00:49:11","Enterocytes play a major role in lipid absorption. In the enterocytes, dietary lipids are packed into chylomicrons and ultimately secreted into the circulation. The dysregulation of chylomicron biogenesis has been linked to various metabolic disorders including obesity. However, the regulation and production of chylomicron is not yet fully understood. Our first study demonstrated that SEC16B, an endoplasmic reticulum (ER) scaffold protein, regulates chylomicron and obesity in vivo. The single-nucleotide polymorphisms (SNPs) in the SEC16B gene have been identified by numerous genome-wide association studies (GWAS) to be associated with obesity and higher body mass index (BMI). Our study showed that Sec16b deletion in mouse intestines, especially in females, alleviates high-fat diet-induced obesity and improves glucose metabolism. We also demonstrated that mice with dysfunctional Sec16b have significantly reduced post-prandial serum triglyceride (TG) contents when orally administered with lipid bolus. Mechanistically, loss of Sec16b impairs apoB-48 lipidation and hinders pre-chylomicron export from the ER. In summary, our first study identified Sec16b as an essential regulator for chylomicron biogenesis and obesity. Enterocytes work in hazardous environments and need constant replenishment. Our second study focuses on the regulation of intestinal epithelium renewal. Intestinal stem cells (ISCs) in crypts drive enterocyte renewal and are regulated by several factors including lipids. A previous study showed increased cholesterol biosynthesis and cellular cholesterol levels stimulate crypt proliferation. However, whether circulating cholesterol will affect ISC proliferation is still unknown. Our results showed that deletion of low-density lipoprotein receptor (LDLR) moderately enhances ISC proliferation. Treating crypts with LDL ex vivo impairs initial organoid formation but enhances the stemness of the surviving organoids. Unexpectedly, Ldlr-/- and wild-type (WT) organoids reacted similarly to LDL treatment, suggesting that the effect of LDL is not dependent on LDLR. Moreover, loss of Ldlr-/- hinders small intestine regeneration. Taken together, these findings underline the complex role of circulating LDL-cholesterol in ISC homeostasis and self-renewal."],"dc:format":["application/pdf"],"dc:identifier":["https://hdl.handle.net/2142/124651"],"dc:language":["en","eng"],"dc:rights":["Copyright 2024 Ruicheng Shi"],"dc:subject":["Small Intestine","Lipid Metabolism","Obesity","Sec16b","Chylomicron","Stem Cell","Regeneration"],"dc:title":["Lipid metabolism and small intestine homeostasis"],"dc:type":["text"],"thesis:degree_discipline":["VMS - Comparative Biosciences"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Ph.D."],"thesis:institution_name":["University of Illinois at Urbana-Champaign"]},"updated_at":"2026-07-22T22:25:02Z"}