Wiley Interdiscip Rev Syst Biol Med - Systems biology of adipose tissue metabolism: regulation of growth, signaling and inflammation.

Tópicos

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Resumo

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.

Resumo Limpo

adipos tissu depot activ regul whole bodi energi homeostasi orchestr complex communic physiolog system well within tissu adipocyt readili respond hormon nutrit input store excess nutrient intracellular lipid mobil store fat util coordin regul metabol pathway balanc uptak esterif hydrolysi lipid accomplish posit negat feedback interact regulatori hub compris sever pleiotrop protein kinas nuclear receptor metabol regul adipocyt encompass biogenesi remodel uniqu larg lipid droplet lds regulatori hub also function energi nutrient sensor integr metabol regul intercellular signal overnutrit caus hypertroph expans adipocyt incomplet understood mechan initi cascad metabol signal event lead tissu remodel immun cell recruit macrophag activ polar toward proinflammatori phenotyp drive selfreinforc cycl proinflammatori signal establish inflammatori state sustain inflamm acceler lipolysi elev free fatti acid circul robust correl develop obesityrel diseas adipos regulatori network coupl metabol growth signal multipl cell type exceed complex compon regulatori network individu studi exquisit detail system approach rare util comprehens assess relat engag compon thus need opportun exist develop quantit model metabol signal network achiev complet understand biolog health diseas

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