Genetic variation in lipid desaturases and its impact on the development of human disease

Abstract

Perturbations in lipid metabolism characterize many of the chronic diseases currently plaguing our society, such as obesity, diabetes, and cardiovascular disease. Thus interventions that target plasma lipid levels remain a primary goal to manage these diseases. The determinants of plasma lipid levels are multi-factorial, consisting of both genetic and lifestyle components. Recent evidence indicates that fatty acid desaturases have an important role in defining plasma and tissue lipid profiles. This review will highlight the current state-of-knowledge regarding three desaturases (Scd-1, Fads1 and Fads2) and their potential roles in disease onset and development. Although research in rodent models has provided invaluable insight into the regulation and functions of these desaturases, the extent to which murine research can be translated to humans remains unclear. Evidence emerging from human-based research demonstrates that genetic variation in human desaturase genes affects enzyme activity and, consequently, disease risk factors. Moreover, this genetic variation may have a trans-generational effect via breastfeeding. Therefore inter-individual variation in desaturase function is attributed to both genetic and lifestyle components. As such, population-based research regarding the role of desaturases on disease risk is challenged by this complex gene-lifestyle paradigm. Unravelling the contribution of each component is paramount for understanding the inter-individual variation that exists in plasma lipid profiles, and will provide crucial information to develop personalized strategies to improve health management.

A distinct adipose tissue gene expression response to caloric restriction predicts 6-mo weight maintenance in obese subjects

“…More specifically, 583 genes were upregulated and 708 were downregulated in the WMs, whereas 628 genes were upregulated and 670 were downregulated in the WRs. The most significant downregulated gene in both WM and WR was stearoyl-CoA desaturase (SCD1; WMs: 23.4-fold; WRs: 22.5-fold), the ratelimiting enzyme responsible for the conversion of SFAs into MUFAs (30). Expression changes for SCD1 were confirmed by real-time RT-PCR (WMs: 21.8-fold; WRs: 22.0-fold; P , 0.05).…”

Fatty Acids as Biocompounds: Their Role in Human Metabolism, Health and Disease - A Review. Part 2: Fatty Acid Physiological Roles and Applications in Human Health and Disease

“…This introduces a nutrigenomics approach to disease control and prevention 7 . Polymorphisms in the genes encoding Δ5-and Δ6-desaturases, FADS1 and FADS2 respectively (chromosome 11q12-11q13.1), have been associated with PUFA and LC PUFA status and cholesterol levels.…”

“…The beneficial effects of breast feeding can be altered by the mother-infant-pair genotype. Gene-diet interactions should be taken into account when investigating the effects of maternal diet on the offspring health 7 .…”

“…Thus, these FA may be characterised as conditionally essential depending on EFA availability. Genetic variation in human desaturase genes affects FA metabolism, plasma lipid profiles, and risk of disease development [5][6][7] . Recommendations for minimum dietary intake of EPA plus DHA vary between 250-450 mg/day 8 , especially for pregnant women and those of reproductive age.…”

The Role of Lipids in Inflammation: Review of the Evolving Pathogenesis of Sickle Cell Disease

“…Previous studies have observed that SNPs and microindels have been implicated in drug metabolism via their encoding gene-CYP2D6 with loss of enzyme activity and slow metabolism [50,51]. Alterations in the FADS enzyme genes are associated with the variations in the activity of these enzymes [52,53] as well as the K-ras gene in some other patient groups. Polymorphism in the genes coding for the FADS enzymes have been discovered in genome wide association studies by Guan et al [54].…”