Department of Chemical and Biological Engineering, Tufts University, Medford, MA, USA.
Wiley Interdiscip Rev Syst Biol Med. 2013 Jul-Aug;5(4):425-47. doi: 10.1002/wsbm.1213. Epub 2013 Feb 13.
Adipose tissue (AT) depots actively regulate whole body energy homeostasis by orchestrating complex communications with other physiological systems as well as within the tissue. Adipocytes readily respond to hormonal and nutritional inputs to store excess nutrients as intracellular lipids or mobilize the stored fat for utilization. Co-ordinated regulation of metabolic pathways balancing uptake, esterification, and hydrolysis of lipids is accomplished through positive and negative feedback interactions of regulatory hubs comprising several pleiotropic protein kinases and nuclear receptors. Metabolic regulation in adipocytes encompasses biogenesis and remodeling of uniquely large lipid droplets (LDs). The regulatory hubs also function as energy and nutrient sensors, and integrate metabolic regulation with intercellular signaling. Over-nutrition causes hypertrophic expansion of adipocytes, which, through incompletely understood mechanisms, initiates a cascade of metabolic and signaling events leading to tissue remodeling and immune cell recruitment. Macrophage activation and polarization toward a pro-inflammatory phenotype drives a self-reinforcing cycle of pro-inflammatory signals in the AT, establishing an inflammatory state. Sustained inflammation accelerates lipolysis and elevates free fatty acids in circulation, which robustly correlates with development of obesity-related diseases. The adipose regulatory network coupling metabolism, growth, and signaling of multiple cell types is exceedingly complex. While components of the regulatory network have been individually studied in exquisite detail, systems approaches have rarely been utilized to comprehensively assess the relative engagements of the components. Thus, need and opportunity exist to develop quantitative models of metabolic and signaling networks to achieve a more complete understanding of AT biology in both health and disease.
脂肪组织（AT）通过与其他生理系统以及组织内的复杂通讯来积极调节全身能量稳态。脂肪细胞容易响应激素和营养输入，将多余的营养物质储存为细胞内脂质，或动员储存的脂肪以供利用。通过包含几种多效性蛋白激酶和核受体的调节枢纽的正反馈和负反馈相互作用，协调代谢途径的平衡，实现脂质的摄取、酯化和水解。脂肪细胞中的代谢调节包括独特的大脂滴（LD）的生物发生和重塑。调节枢纽还作为能量和营养传感器，将代谢调节与细胞间信号传递整合在一起。营养过剩导致脂肪细胞肥大扩张，通过尚未完全了解的机制，引发一系列代谢和信号事件，导致组织重塑和免疫细胞募集。巨噬细胞的激活和向促炎表型的极化驱动了 AT 中促炎信号的自我增强循环，建立了炎症状态。持续的炎症加速脂肪分解并增加循环中的游离脂肪酸，这与肥胖相关疾病的发展密切相关。耦合代谢、生长和多种细胞类型信号的脂肪调节网络极其复杂。虽然已经单独对调节网络的组成部分进行了精细的研究，但很少利用系统方法全面评估各组成部分的相对参与情况。因此，需要并有可能开发代谢和信号网络的定量模型，以更全面地了解健康和疾病状态下 AT 的生物学。
