脂解
内科学
内分泌学
激素
胰岛素
生物
基础(医学)
脂肪组织
化学
医学
作者
Karen Inouye,Kacey J. Prentice,Alexandra Lee,Carla Dominguez-Gonzalez,Mu Xian Chen,Grace Yankun Lee,Gökhan S. Hotamışlıgil
标识
DOI:10.1101/2022.10.13.511807
摘要
Abstract Fatty acid binding protein 4 (FABP4) is a lipid chaperone secreted from adipocytes upon stimulation of lipolysis. Circulating FABP4 levels strongly correlate with body mass index and obesity-related pathologies in experimental models and humans. While adipocytes have been presumed to be the major source of hormonal FABP4, this question has not been addressed definitively in vivo . We generated mice with FABP4 deletion in cells known to express the gene; adipocytes (Adipo-KO), endothelial cells (Endo-KO), myeloid cells (Myeloid-KO), and the whole body (Total-KO) to examine the contribution of these cell types to basal and stimulated plasma FABP4 levels. Unexpectedly, baseline plasma FABP4 was only reduced by ∼25% in Adipo-KO mice, whereas Endo-KO mice showed ∼75% decreases compared to wildtype controls. In contrast, Adipo-KO mice exhibited ∼62% reduction in FABP4 responses to lipolysis, while there was minimal reduction in Endo-KO mice, indicating that adipocytes are the main FABP4 source in lipolysis. We did not detect any myeloid cell contribution to circulating FABP4. Surprisingly, despite the nearly intact FABP4 responses, Endo-KO mice showed blunted lipolysis-induced insulin secretion, identical to Total-KO mice. We conclude that the endothelium is the major source of baseline hormonal FABP4 and is required for the insulin response to lipolysis.
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