Exploring the unique effects of α-linolenic acid and docosahexaenoic acid on mononuclear immune cell gene expression and function: implications for obesity and atherosclerosis
| dc.contributor.author | Rodway, Lisa | |
| dc.contributor.examiningcommittee | Czubryt, Michael (Physiology & Pathophysiology) | en_US |
| dc.contributor.examiningcommittee | Aukema, Harold (Food and Human Nutritional Sciences) | en_US |
| dc.contributor.supervisor | Zahradka, Peter (Physiology & Pathophysiology) Taylor, Carla (Food and Human Nutritional Sciences) | en_US |
| dc.date.accessioned | 2022-02-07T21:12:53Z | |
| dc.date.available | 2022-02-07T21:12:53Z | |
| dc.date.copyright | 2022-02-07 | |
| dc.date.issued | 2022-01-25 | en_US |
| dc.date.submitted | 2022-01-27T20:08:53Z | en_US |
| dc.date.submitted | 2022-02-07T19:55:34Z | en_US |
| dc.date.submitted | 2022-02-07T20:32:20Z | en_US |
| dc.degree.discipline | Physiology and Pathophysiology | en_US |
| dc.degree.level | Master of Science (M.Sc.) | en_US |
| dc.description.abstract | Background: Monocytes play a central role in chronic inflammatory conditions such as obesity and atherosclerosis. Marine-derived omega-3 fatty acids (n-3 PUFAs) such as docosahexaenoic acid (DHA) have been shown to beneficially alter immune function and attenuate chronic inflammation in part by altering immune cell gene expression. Comparisons to the plant-derived n-3 PUFA, α-linolenic acid (ALA), on immune cell gene expression and function are limited. Methods: Whole transcriptome analysis using a Clariom D microarray was performed on total mRNA isolated from a human THP-1 monocyte cell line treated with ALA, DHA or vehicle equivalent for 48 hr. Candidate genes (those responding to n-3 PUFA treatment) were identified via fold change and Ingenuity Pathway Analysis, and transcripts were subsequently validated by RT-qPCR. Assays to measure total cholesterol content and migration in response to chemokine (chemotaxis) were then performed on THP-1 monocytes treated with ALA or DHA to evaluate the outcomes of transcriptomic predictions. Candidate mRNA transcripts were examined via RT-qPCR in mononuclear immune cells isolated from a subgroup of clinical trial participants, where women with obesity received 4 g/day DHA or ALA for 4 weeks each. Results & Conclusion: In THP-1 monocytes, transcriptome analysis identified ALA and DHA treatment differentially altered gene expression associated with cholesterol metabolism and chemotaxis. Based on these data, cholesterol content was predicted to be reduced by both fatty acids, while ALA would uniquely increase chemotaxis and DHA would have no effect. Functional assays revealed that ALA and DHA decreased cholesterol content to a similar extent. In contrast to our predictions, DHA significantly decreased chemotaxis, while ALA had no effect. Mononuclear immune cells obtained from a clinical n-3 PUFA supplementation trial displayed similar expression patterns to candidate transcripts identified in fatty acid treated THP-1 monocytes. Taken together, these results demonstrate that ALA and DHA differentially alter gene expression and cellular functions associated with chemotaxis and cholesterol metabolism in mononuclear immune cells. Thus, they may uniquely affect related disease processes contributing to obesity and atherosclerosis. | en_US |
| dc.description.note | March 2022 | en_US |
| dc.identifier.uri | http://hdl.handle.net/1993/36285 | |
| dc.language.iso | eng | en_US |
| dc.rights | open access | en_US |
| dc.subject | Obesity | en_US |
| dc.subject | Atherosclerosis | en_US |
| dc.subject | Gene Expression | en_US |
| dc.subject | Monocytes | en_US |
| dc.subject | Immune Function | en_US |
| dc.subject | Omega-3 Fatty Acids | en_US |
| dc.title | Exploring the unique effects of α-linolenic acid and docosahexaenoic acid on mononuclear immune cell gene expression and function: implications for obesity and atherosclerosis | en_US |
| dc.type | master thesis | en_US |