University of Guelph, Department of Human Health & Nutritional Sciences, Guelph N1G 2W1, Canada.
Lipids Health Dis. 2010 Jun 18;9:63. doi: 10.1186/1476-511X-9-63.
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.
脂质代谢的紊乱是目前困扰我们社会的许多慢性疾病的特征，如肥胖、糖尿病和心血管疾病。因此，靶向血浆脂质水平的干预仍然是管理这些疾病的主要目标。血浆脂质水平的决定因素是多因素的，包括遗传和生活方式因素。最近的证据表明，脂肪酸去饱和酶在定义血浆和组织脂质谱方面起着重要作用。这篇综述将重点介绍三种去饱和酶（Scd-1、Fads1 和 Fads2）的最新知识及其在疾病发病和发展中的潜在作用。尽管啮齿动物模型的研究为这些去饱和酶的调节和功能提供了宝贵的见解，但啮齿动物研究在多大程度上可以转化为人类仍然不清楚。来自基于人类的研究的证据表明，人类去饱和酶基因的遗传变异影响酶活性，进而影响疾病风险因素。此外，这种遗传变异可能通过母乳喂养产生跨代效应。因此，去饱和酶功能的个体差异归因于遗传和生活方式因素。因此，由于这种复杂的基因-生活方式范式，关于去饱和酶在疾病风险中的作用的基于人群的研究受到了挑战。揭示每个组成部分的贡献对于理解血浆脂质谱中存在的个体间差异至关重要，并将为制定个性化策略以改善健康管理提供重要信息。
