| First Author | Stoffel W | Year | 2014 |
| Journal | EMBO Rep | Volume | 15 |
| Issue | 1 | Pages | 110-20 |
| PubMed ID | 24378641 | Mgi Jnum | J:211959 |
| Mgi Id | MGI:5577021 | Doi | 10.1002/embr.201338041 |
| Citation | Stoffel W, et al. (2014) Obesity resistance and deregulation of lipogenesis in Delta6-fatty acid desaturase (FADS2) deficiency. EMBO Rep 15(1):110-20 |
| abstractText | Delta-6-fatty acid desaturase (FADS2) is the key enzyme in the biosynthesis of polyunsaturated fatty acids (PUFAs), the essential structural determinants of mammalian membrane lipid-bilayers. We developed the auxotrophic fads2(-/-) mouse mutant to assess the enigmatic role of omega3- and omega6-PUFAs in lipid homeostasis, membrane structure and function. Obesity resistance is another major phenotype of the fads2(-/-) mutant, the molecular basis of which is unknown. Phospholipidomic profiling of membrane systems of fads2(-/-)mice revealed diacylglycerol-structures, deprived of PUFAs but substituted with surrogate eicosa-5,11,14-trienoic acid. omega6-Arachidonic (AA) and omega3-docosahexaenoic acid (DHA) supplemented diets transformed fads2(-/-) into AA-fads2(-/-) and DHA-fads2(-/-) mutants. Severely altered phospholipid-bilayer structures of subcellular membranes of fads2(-/-) liver specifically interfered with maturation of transcription factor sterol-regulatory-element-binding protein, the key regulator of lipogenesis and lipid homeostasis. This study strengthens the concept that specific PUFA-substituted membrane phospholipid species are critical constituents of the structural platform operative in lipid homeostasis in normal and disease conditions. |
