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ELOVL2 and PUFA biosynthesis: Impact on sex-specific processes in mammals
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. (Anders Jacobsson)
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Endogenously synthesized PUFAs (Polyunsaturated Fatty Acids) vary in production depending on medical conditions, gender, developmental phase, age, fertility status, pregnancy and lactation. PUFA biosynthesis is further regulated via amount of dietary intake as well as genetically. A key player in the PUFA biosynthesis enzyme machinery is the fatty acid elongase Elongation of very long-chain fatty acids 2 (ELOVL2) that is essential for the production of the omega-3 PUFA docosahexaenoic acid (DHA, 22:6 n-3) that has many beneficial health effects. In the omega-6 PUFA series, ELOVL2 produces docosapentaenoic acid (DPA n-6, 22:5 n-6). Specifically, ELOVL2 enables the elongation of PUFA with 22 carbons to generate precursors of 24 carbons for the generation of the previously mentioned end products as well as very long-chain (VLC) PUFA up to C34.

This thesis elucidates that estrogen has the power to modulate ELOVL2 expression in breast cancer cells and that this probably is due to ligand dependent binding of the estrogen receptor alpha (ERα) to the Elovl2 enhancer. In addition, estrogen via ERα modulates hepatic levels of Elovl2 in mice in a gender specific manner. Ablation of Elovl2 leads to whole body deficiency of DHA. The thesis unravels that systemic DHA levels in neonatal mice is determined both by the ELOVL2 status of the mother and the offspring. Ablation of Elovl2 also leads to impaired spermatogenesis and infertility in male mice. However, heterozygous Elovl2-ablated mice, differ in fertility potency depending on strain. Here we show that this discrepancy is linked to an altered ratio between saturated and mono-unsaturated fatty acids and VLC-PUFA moieties of glucosylceramides in testis.

Place, publisher, year, edition, pages
Stockholm: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University , 2016. , 64 p.
National Category
Biophysics
Research subject
Physiology
Identifiers
URN: urn:nbn:se:su:diva-134356ISBN: 978-91-7649-549-0ISBN: 978-91-7649-550-6OAI: oai:DiVA.org:su-134356DiVA: diva2:1033054
Public defence
2016-11-15, Vivi Täckholmsalen (Q-salen), NPQ-huset, Svante Arrhenius väg 20, Stockholm, 10:00 (English)
Opponent
Supervisors
Note

At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 1: Accepted. Paper 2: Manuscript. Paper 3: Manuscript. Paper 4: Manuscript.

Available from: 2016-10-21 Created: 2016-10-05 Last updated: 2016-10-25Bibliographically approved
List of papers
1. Estrogen Enhances the Expression of the Poly-Unsaturated Fatty Acid Elongase Elovl2 via ERα in Breast Cancer Cells
Open this publication in new window or tab >>Estrogen Enhances the Expression of the Poly-Unsaturated Fatty Acid Elongase Elovl2 via ERα in Breast Cancer Cells
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(English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203Article in journal (Refereed) Accepted
National Category
Biological Sciences
Research subject
Physiology
Identifiers
urn:nbn:se:su:diva-134358 (URN)
Available from: 2016-10-05 Created: 2016-10-05 Last updated: 2016-10-18
2. Sex differences in the control of PUFA-synthesizing enzymes by estrogen in mice
Open this publication in new window or tab >>Sex differences in the control of PUFA-synthesizing enzymes by estrogen in mice
(English)Manuscript (preprint) (Other academic)
National Category
Biological Sciences
Research subject
Physiology
Identifiers
urn:nbn:se:su:diva-134359 (URN)
Available from: 2016-10-05 Created: 2016-10-05 Last updated: 2016-10-18Bibliographically approved
3. Both maternal and offspring Elovl2 genotypes determine systemic DHA levels in perinatal mice
Open this publication in new window or tab >>Both maternal and offspring Elovl2 genotypes determine systemic DHA levels in perinatal mice
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(English)Manuscript (preprint) (Other academic)
National Category
Biological Sciences
Research subject
Physiology
Identifiers
urn:nbn:se:su:diva-134086 (URN)
Available from: 2016-09-30 Created: 2016-09-30 Last updated: 2016-10-06Bibliographically approved
4. Elovl2 haploinsufficient C57Bl/6 but not 129/Sv mice are infertile due to impaired levels of glucosylceramide fatty acid moities in testis
Open this publication in new window or tab >>Elovl2 haploinsufficient C57Bl/6 but not 129/Sv mice are infertile due to impaired levels of glucosylceramide fatty acid moities in testis
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(English)Manuscript (preprint) (Other academic)
National Category
Biological Sciences
Research subject
Physiology
Identifiers
urn:nbn:se:su:diva-134360 (URN)
Available from: 2016-10-05 Created: 2016-10-05 Last updated: 2016-10-18Bibliographically approved

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