Oresic Matej
VTT Technical Research Centre of Finland, Tietotie 2, P.O. Box 1000, Espoo, FIN-02044 VTT, Finland.
Biochim Biophys Acta. 2010 Mar;1801(3):235-9. doi: 10.1016/j.bbalip.2009.11.003. Epub 2009 Nov 26.
Systems biology views and studies the biological systems in the context of complex interactions between their building blocks and processes. Given its multi-level complexity, metabolic syndrome (MetS) makes a strong case for adopting the systems biology approach. Despite many MetS traits being highly heritable, it is becoming evident that the genetic contribution to these traits is mediated via gene-gene and gene-environment interactions across several spatial and temporal scales, and that some of these traits such as lipotoxicity may even be a product of long-term dynamic changes of the underlying genetic and molecular networks. This presents several conceptual as well as methodological challenges and may demand a paradigm shift in how we study the undeniably strong genetic component of complex diseases such as MetS. The argument is made here that for adopting systems biology approaches to MetS an integrative framework is needed which glues the biological processes of MetS with specific physiological mechanisms and principles and that lipotoxicity is one such framework. The metabolic phenotypes, molecular and genetic networks can be modeled within the context of such integrative framework and the underlying physiology.
系统生物学从生物系统的组成部分和过程之间复杂的相互作用角度来观察和研究这些系统。鉴于代谢综合征（MetS）具有多层次的复杂性，采用系统生物学方法来研究它具有充分的理由。尽管许多代谢综合征特征具有高度遗传性，但越来越明显的是，对这些特征的遗传贡献是通过跨越多个空间和时间尺度的基因-基因和基因-环境相互作用来介导的，而且其中一些特征，如脂毒性，甚至可能是潜在遗传和分子网络长期动态变化的产物。这带来了一些概念和方法上的挑战，可能需要我们在研究诸如代谢综合征等复杂疾病中不可否认的强大遗传成分的方式上进行范式转变。这里的观点是，为了将系统生物学方法应用于代谢综合征，需要一个整合框架，将代谢综合征的生物学过程与特定的生理机制和原理联系起来，而脂毒性就是这样一个框架。代谢表型、分子和遗传网络可以在这样的整合框架和潜在生理学背景下进行建模。
