Effects of the postprandial environment on the unfolded protein response
| dc.contributor.author | Pfaffenbach, Kyle, author | |
| dc.contributor.author | Pagliassotti, Michael J., advisor | |
| dc.date.accessioned | 2024-03-13T20:12:30Z | |
| dc.date.available | 2024-03-13T20:12:30Z | |
| dc.date.issued | 2009 | |
| dc.description.abstract | Background and specific aims. Newly synthesized proteins must undergo post-translational modifications such as folding and glycosylation to become fully functional. The lumen of the endoplasmic reticulum (ER) is a major site of protein folding and processing. The ER can respond to an increase in unfolded proteins (termed "ER stress") by activating the Unfolded Protein Response (UPR), a quality control mechanism which maintains ER homeostasis. Recent studies have demonstrated that the UPR is also involved in the regulation of a diverse array of cellular processes including glucose homeostasis, lipogenesis, and protein synthesis. The liver plays a central role in nutrient metabolism and maintaining glucose homeostasis. Further, in the postprandial state, both lipogenesis and protein synthesis are stimulated in the liver. However, the role of the UPR in the postprandial regulation of these processes has not been studied. Therefore, the first aim of the present study was to examine and characterize the regulation of the UPR in the postprandial state in the liver. One of the main rate limiting steps in protein synthesis is regulated by the mammalian target of rapamycin complex-I (mTORC I). Thus, the second aim of the current study was to examine the role of mTORC1 in the postprandial regulation of the UPR. Methods. Rats in Study 1 were fed a single starch or high sucrose meal and sacrificed either 1 or 7 hours post-feeding period. Plasma glucose and insulin were measured and hepatic tissue was examined for markers of UPR activation. Rats in Study 2 were injected with rapamycin, an inhibitor of mTORC1, prior to meal feeding. Rats were sacrificed 1 or 7 hours post-feeding period and blood and liver tissue were collected for analysis. To examine the role of insulin and glucose in the postprandial activation of the UPR H4IIE liver cells were exposed to varying amounts of glucose and insulin in the presence or absence of rapamycin. Results. Feeding activated select components of the UPR, including spliced X-box binding protein-1 (XBP1) and increased GRP78 and GRP94 mRNA expression. Rapamycin inhibited the postprandial increase of these components. The phosphorylation of eif2-α protein was not increased postprandially in the liver. Data from H4IIE cells demonstrate that insulin in the presence of glucose can activate UPR components in an mTORC1 dependent manner. Conclusion. The current study demonstrates that select components of the UPR are activated in the liver in the postprandial state. This activation appears to be insulin and mTORC1 dependent. | |
| dc.format.medium | born digital | |
| dc.format.medium | doctoral dissertations | |
| dc.identifier | ETDF_Pfaffenbach_2009_3374613.pdf | |
| dc.identifier.uri | https://hdl.handle.net/10217/237908 | |
| dc.language | English | |
| dc.language.iso | eng | |
| dc.publisher | Colorado State University. Libraries | |
| dc.relation.ispartof | 2000-2019 | |
| dc.rights | Copyright and other restrictions may apply. User is responsible for compliance with all applicable laws. For information about copyright law, please see https://libguides.colostate.edu/copyright. | |
| dc.rights.license | Per the terms of a contractual agreement, all use of this item is limited to the non-commercial use of Colorado State University and its authorized users. | |
| dc.subject | ER stress | |
| dc.subject | postprandial | |
| dc.subject | unfolded protein response | |
| dc.subject | nutrition | |
| dc.title | Effects of the postprandial environment on the unfolded protein response | |
| dc.type | Text | |
| dcterms.rights.dpla | This Item is protected by copyright and/or related rights (https://rightsstatements.org/vocab/InC/1.0/). You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s). | |
| thesis.degree.discipline | Food Science and Human Nutrition | |
| thesis.degree.grantor | Colorado State University | |
| thesis.degree.level | Doctoral | |
| thesis.degree.name | Doctor of Philosophy (Ph.D.) |
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