PDF(Pubmed)
Abstract：
Excessive adiposity in obesity is a significant risk factor for development of type 2 diabetes (T2D), nonalcoholic fatty liver disease, and other cardiometabolic diseases. An unhealthy expansion of adipose tissue (AT) results in reduced adipogenesis, increased adipocyte hypertrophy, adipocyte hypoxia, chronic low-grade inflammation, increased macrophage infiltration, and insulin resistance. This ultimately culminates in AT dysfunction characterized by decreased secretion of antidiabetic adipokines such as adiponectin and adipsin and increased secretion of proinflammatory prodiabetic adipokines including RBP4 and resistin. This imbalance in adipokine secretion alters the physiological state of AT communication with target organs including pancreatic β-cells, heart, and liver. In the pancreatic β-cells, adipokines are known to have a direct effect on insulin secretion, gene expression, cell death, and/or dedifferentiation. For instance, impaired secretion of adipsin, which promotes insulin secretion and β-cell identity, results in β-cell failure and T2D, thus presenting a potential druggable target to improve and/or preserve β-cell function. The cardiac tissue is affected by both the classic white AT-secreted adipokines and the newly recognized brown AT (BAT)-secreted BATokines or lipokines that alter lipid deposition and ventricular function. In the liver, adipokines affect hepatic gluconeogenesis, lipid accumulation, and insulin sensitivity, underscoring the importance of adipose-liver communication in the pathogenesis of nonalcoholic fatty liver disease. In this perspective, we outline what is currently known about the effects of individual adipokines on pancreatic β-cells, liver, and the heart.
摘要：
肥胖中的过度肥胖是2型糖尿病（T2D）发展的重要危险因素，非酒精性脂肪性肝病,和其他心脏代谢疾病。脂肪组织（AT）的不健康扩张导致脂肪生成减少，脂肪细胞肥大增加，脂肪细胞缺氧,慢性低度炎症，巨噬细胞浸润增加，和胰岛素抵抗。这最终导致AT功能障碍,其特征在于抗糖尿病脂肪因子如脂联素和脂肪素的分泌减少,以及包括RBP4和抵抗素的促炎性前糖尿病脂肪因子的分泌增加。脂肪因子分泌的这种失衡改变了AT与靶器官（包括胰腺β细胞）通讯的生理状态。心,还有肝脏.在胰腺β细胞中，已知脂肪因子对胰岛素分泌有直接影响，基因表达，细胞死亡,和/或去分化。例如,脂肪素分泌受损，促进胰岛素分泌和β细胞同一性，导致β细胞衰竭和T2D，因此提出了一个潜在的药物靶标，以改善和/或保持β细胞功能。心脏组织受经典的白色AT分泌的脂肪因子和新发现的棕色AT（BAT）分泌的BATokines或脂质因子的影响，这些因子会改变脂质沉积和心室功能。在肝脏中，脂肪因子影响肝糖异生，脂质积累，和胰岛素敏感性，强调脂肪肝通讯在非酒精性脂肪性肝病发病机制中的重要性。从这个角度来看,我们概述了目前已知的关于单个脂肪因子对胰腺β细胞的影响，肝脏,还有心脏.
