Hilton Catriona, Karpe Fredrik, Pinnick Katherine E
Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, OUH Trust, Churchill Hospital, Oxford, UK.
Biochim Biophys Acta. 2015 May;1851(5):686-96. doi: 10.1016/j.bbalip.2015.02.003. Epub 2015 Feb 8.
In this review we discuss the role of developmental transcription factors in adipose tissue biology with a focus on how these developmental genes may contribute to regional variation in adipose tissue distribution and function. Regional, depot-specific, differences in lipid handling and signalling (lipolysis, lipid storage and adipokine/lipokine signalling) are important determinants of metabolic health. At a cellular level, preadipocytes removed from their original depot and cultured in vitro retain depot-specific functional properties, implying that these are intrinsic to the cells and not a function of their environment in situ. High throughput screening has identified a number of developmental transcription factors involved in embryological development, including members of the Homeobox and T-Box gene families, that are strongly differentially expressed between regional white adipose tissue depots and also between brown and white adipose tissue. However, the significance of depot-specific developmental signatures remains unclear. Developmental transcription factors determine body patterning during embryogenesis. The divergent developmental origins of regional adipose tissue depots may explain their differing functional characteristics. There is evidence from human genetics that developmental genes determine adipose tissue distribution: in GWAS studies a number of developmental genes have been identified as being correlated with anthropometric measures of adiposity and fat distribution. Additionally, compelling functional studies have recently implicated developmental genes in both white adipogenesis and the so-called 'browning' of white adipose tissue. Understanding the genetic and developmental pathways in adipose tissue may help uncover novel ways to intervene with the function of adipose tissue in order to promote health.
在本综述中，我们讨论发育转录因子在脂肪组织生物学中的作用，重点关注这些发育基因如何导致脂肪组织分布和功能的区域差异。脂质处理和信号传导（脂解、脂质储存和脂肪因子/脂质因子信号传导）的区域特异性差异是代谢健康的重要决定因素。在细胞水平上，从其原始储存部位取出并在体外培养的前脂肪细胞保留了储存部位特异性的功能特性，这意味着这些特性是细胞固有的，而非其原位环境的功能。高通量筛选已鉴定出许多参与胚胎发育的发育转录因子，包括同源框基因家族和T盒基因家族的成员，这些转录因子在区域白色脂肪组织储存部位之间以及棕色和白色脂肪组织之间存在强烈的差异表达。然而，储存部位特异性发育特征的意义仍不清楚。发育转录因子在胚胎发生过程中决定身体模式。区域脂肪组织储存部位不同的发育起源可能解释了它们不同的功能特征。人类遗传学证据表明，发育基因决定脂肪组织分布：在全基因组关联研究中，已鉴定出许多发育基因与肥胖和脂肪分布的人体测量指标相关。此外，最近引人注目的功能研究表明，发育基因在白色脂肪生成和白色脂肪组织的所谓“褐变”中均起作用。了解脂肪组织中的遗传和发育途径可能有助于发现干预脂肪组织功能以促进健康的新方法。
