Influence of genetic variants in FADS2 and ELOVL2 genes on BMI and PUFAs homeostasis in children and adolescents with obesity

Maguolo, Alice; Zusi, Chiara; Giontella, Alice; Giudice, Emanuele Miraglia del; Tagetti, Angela; Fava, Cristiano; Morandi, Anita; Maffeis, Claudio

doi:10.1038/s41366-020-00662-9

Cited by 23 publications

(17 citation statements)

References 96 publications

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“…The knowledge presented here implies that endogenous long-chain PUFA production is vital for mice and human metabolism. Our findings are underlying several other studies on identifying genetic variants in the ELOVL2 gene associated with obesity-related conditions [7][8][9]. Dietetics and scholars need to consider interindividual genetic variability in endogenous PUFA modification in humans coupled with PUFA derived from the diet when the relationship between PUFA intake and effects is investigated.…”

Section: The Physiological Value Of Long Chain Pufas As Nutrientssupporting

confidence: 67%

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Elovl2-Ablation Leads to Mitochondrial Membrane Fatty Acid Remodeling and Reduced Efficiency in Mouse Liver Mitochondria

et al. 2022

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The fatty acid elongase elongation of very long-chain fatty acids protein 2 (ELOVL2) controls the elongation of polyunsaturated fatty acids (PUFA) producing precursors for omega-3, docosahexaenoic acid (DHA), and omega-6, docosapentaenoic acid (DPAn6) in vivo. Expectedly, Elovl2-ablation drastically reduced the DHA and DPAn6 in liver mitochondrial membranes. Unexpectedly, however, total PUFAs levels decreased further than could be explained by Elovl2 ablation. The lipid peroxidation process was not involved in PUFAs reduction since malondialdehyde-lysine (MDAL) and other oxidative stress biomarkers were not enhanced. The content of mitochondrial respiratory chain proteins remained unchanged. Still, membrane remodeling was associated with the high voltage-dependent anion channel (VDAC) and adenine nucleotide translocase 2 (ANT2), a possible reflection of the increased demand on phospholipid transport to the mitochondria. Mitochondrial function was impaired despite preserved content of the respiratory chain proteins and the absence of oxidative damage. Oligomycin-insensitive oxygen consumption increased, and coefficients of respiratory control were reduced by 50%. The mitochondria became very sensitive to fatty acid-induced uncoupling and permeabilization, where ANT2 is involved. Mitochondrial volume and number of peroxisomes increased as revealed by transmission electron microscopy. In conclusion, the results imply that endogenous DHA production is vital for the normal function of mouse liver mitochondria and could be relevant not only for mice but also for human metabolism.

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Section: The Physiological Value Of Long Chain Pufas As Nutrientssupporting

confidence: 67%

“…Nutrients 2022, 14, 559 2 of 18 Several studies have identified the association between genetic variants in the FADS2 and ELOVL2 genes controlling endogenous PUFA synthesis and obesity-related conditions in adults and children [7][8][9]. However, the underlying mechanism connecting genetics and metabolism remains unknown.…”

Section: Introductionmentioning

confidence: 99%

Elovl2-Ablation Leads to Mitochondrial Membrane Fatty Acid Remodeling and Reduced Efficiency in Mouse Liver Mitochondria

et al. 2022

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“…In a study carried out in a population of Tunisia, in which two SNPs of desaturases (FAD1 and FAD2) and one of ELOVL2 (rs3756963) were analyzed, the authors observed that the minor allele C is related to low triglyceride levels and low body mass index, which confers a protective factor to the population with this variant [41]. Similarly, in another study carried out in Italian children and adolescents, a similar behavior was observed in the association of genetic variants of ELOVL2 with indicators of obesity and insulin resistance, in addition to alterations in the blood lipid profile [42]. Like the aforementioned authors, our results show an important association of ELOVL2 with markers of insulin resistance and elevated total cholesterol, which indicates the value of a larger study to specifically identify the role of this enzyme in the pathophysiology of chronic non-communicable diseases.…”

Section: Discussionmentioning

confidence: 69%

Influence of Single Nucleotide Polymorphisms of ELOVL on Biomarkers of Metabolic Alterations in the Mexican Population

et al. 2020

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The elongation of very long chain fatty acids (ELOVL) is a family of seven enzymes that have specific functions in the synthesis of fatty acids. Some have been shown to be related to insulin secretion (ELOVL2), and in the lipid profile (ELOVL6) and patients with various pathologies. The present work focused on the study of ELOVL polymorphs with clinical markers of non-communicable chronic diseases in the Mexican population. A sample of 1075 participants was obtained, who underwent clinical, biochemical, and nutritional evaluation, and a genetic evaluation of 91 genetic variants of ELOVL was considered (2–7). The results indicate a 33.16% prevalence of obesity by body mass index, 13.84% prevalence of insulin resistance by homeostatic model assessment (HOMA) index, 7.85% prevalence of high cholesterol, and 20.37% prevalence of hypercholesterolemia. The deprived alleles showed that there is no association between them and clinical disease risk markers, and the notable finding of the association studies is that the ELOVL2 variants are exclusive in men and ELVOL7 in women. There is also a strong association of ELOVL6 with various markers. The present study shows, for the first time, the association between the different ELOVLs and clinical markers of chronic non-communicable diseases.

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“…Several studies have identified the association between genetic variants in the FADS2 and ELOVL2 genes controlling endogenous PUFA synthesis and obesity-related conditions in adults and children [7][8][9]. However, the underlying mechanism connecting genetics and metabolism remains unknown.…”

Section: Introductionmentioning

confidence: 99%

Elovl2-Ablation Leads to Mitochondrial Membrane Fatty Acid Remodeling and Reduced Efficiency in Mouse Liver Mitochondria

Rodríguez¹,

Talamonti²,

Naudí³

et al. 2021

Preprint

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The fatty acid elongase ELOngation of Very-Long-chain fatty acids protein 2 (ELOVL2) controls the elongation of polyunsaturated fatty acids (PUFA) producing precursors for omega-3, do-cosahexaenoic acid (DHA), and omega-6, docosapentaenoic acid (DPAn6) in-vivo. Expectedly, Elovl2-ablation drastically reduced the DHA and DPAn6 in liver mitochondrial membranes. Unexpectedly, however, total PUFAs levels decreased further than could be explained by Elovl2 ablation. The lipid peroxidation process was not involved in PUFAs reduction since malondial-dehyde-lysine (MDAL) and other oxidative stress biomarkers were not enhanced. The content of mitochondrial respiratory chain proteins remained unchanged. Still, membrane remodeling was associated with high voltage-dependent anion channel (VDAC) and adenine nucleotide trans-locase 2 (ANT2), a possible reflection of the increased demand on phospholipid transport to the mitochondria. Mitochondrial function was impaired despite preserved content of the respiratory chain proteins and the absence of oxidative damage. Oligomycin-insensitive oxygen consumption increased, and coefficients of respiratory control were reduced by 50%. The mitochondria became very sensitive to fatty acid-induced uncoupling and permeabilization, where ANT2 is involved. Mitochondrial volume and number of peroxisomes increased as revealed by transmission elec-tron microscopy. In conclusion, the results imply that endogenous DHA production is vital for the normal function of mouse liver mitochondria and could be relevant not only for mice but also for human metabolism.

show abstract

Influence of genetic variants in FADS2 and ELOVL2 genes on BMI and PUFAs homeostasis in children and adolescents with obesity

Cited by 23 publications

References 96 publications

Elovl2-Ablation Leads to Mitochondrial Membrane Fatty Acid Remodeling and Reduced Efficiency in Mouse Liver Mitochondria

Elovl2-Ablation Leads to Mitochondrial Membrane Fatty Acid Remodeling and Reduced Efficiency in Mouse Liver Mitochondria

Influence of Single Nucleotide Polymorphisms of ELOVL on Biomarkers of Metabolic Alterations in the Mexican Population

Elovl2-Ablation Leads to Mitochondrial Membrane Fatty Acid Remodeling and Reduced Efficiency in Mouse Liver Mitochondria

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