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The metabolic features induced by FADS mutations from human populations transposed to cell systems

Grant number: 22/00542-7
Support Opportunities:Scholarships abroad - Research
Effective date (Start): August 12, 2022
Effective date (End): August 11, 2023
Field of knowledge:Health Sciences - Nutrition - Nutrition Biochemistry
Principal Investigator:Dennys Esper Corrêa Cintra
Grantee:Dennys Esper Corrêa Cintra
Host Investigator: Rasmus Nielsen
Host Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil
Research place: University of California, Berkeley (UC Berkeley), United States  

Abstract

Omega-3 (w3) and omega-6 (w6) are essential fatty acids for mammals and need to be acquired from foods. In vegetable oils, the w6 and w3 species are found as linoleic (C18:2) and alpha-linolenic (C18:3) fatty acids, respectively. Both fatty acids can be endogenously bioconverted in a more biologically active and functional longer species such as the arachidonic (C20:4 [w6]) and eicosapentaenoic (C20:5 [w3]) and docosahexaenoic (C22:6 [w3]) fatty acids. These processes are dependent on delta-5 and delta-6 desaturase enzymes, respectively encoded by FADS1 and FADS2 (fatty acid desaturases 1/2) genes. Mutations on these genes could impact positively or negatively these biochemical routes. Several polymorphisms (SNP) on FADS1 and FADS2 have been described and found in populations all over the planet, however, occurring in a specific manner under environmental pressure. In the south of Asia, an ancestral FADS2 SNP increased the long-chain fatty acids adapting people to a more vegetarian diet, while Inuits from Greenland were adapted to survive under extremely cold temperatures with a less functional FADS2. The high incidence of SNPs on FADS genes since the beginning of the human migratory trajectory on earth has been considered a significant gene signature of adaptation. Thus, this project aims to transpose the human mutations, evidenced in FADS1 and FADS2 to cellular models, to try to understand, measure, and confirm the possible outcomes. (AU)

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