| Autor: |
Inouye KE; Sabri Ülker Center for Metabolic Research, Harvard T.H. Chan School of Public Health, Department of Molecular Metabolism, Boston, Massachusetts, USA., Prentice KJ; Sabri Ülker Center for Metabolic Research, Harvard T.H. Chan School of Public Health, Department of Molecular Metabolism, Boston, Massachusetts, USA., Lee A; Sabri Ülker Center for Metabolic Research, Harvard T.H. Chan School of Public Health, Department of Molecular Metabolism, Boston, Massachusetts, USA., Wang ZB; Sabri Ülker Center for Metabolic Research, Harvard T.H. Chan School of Public Health, Department of Molecular Metabolism, Boston, Massachusetts, USA., Dominguez-Gonzalez C; Sabri Ülker Center for Metabolic Research, Harvard T.H. Chan School of Public Health, Department of Molecular Metabolism, Boston, Massachusetts, USA., Chen MX; Sabri Ülker Center for Metabolic Research, Harvard T.H. Chan School of Public Health, Department of Molecular Metabolism, Boston, Massachusetts, USA., Riveros JK; Sabri Ülker Center for Metabolic Research, Harvard T.H. Chan School of Public Health, Department of Molecular Metabolism, Boston, Massachusetts, USA., Burak MF; Sabri Ülker Center for Metabolic Research, Harvard T.H. Chan School of Public Health, Department of Molecular Metabolism, Boston, Massachusetts, USA., Lee GY; Sabri Ülker Center for Metabolic Research, Harvard T.H. Chan School of Public Health, Department of Molecular Metabolism, Boston, Massachusetts, USA., Hotamışlıgil GS; Sabri Ülker Center for Metabolic Research, Harvard T.H. Chan School of Public Health, Department of Molecular Metabolism, Boston, Massachusetts, USA.; Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA. |
| Abstrakt: |
Fatty acid binding protein 4 (FABP4) is a lipid chaperone secreted from adipocytes upon stimulation of lipolysis. Circulating FABP4 levels strongly correlate with obesity and metabolic 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 not significantly reduced in Adipo-KO mice, whereas Endo-KO mice showed ~87% reduction versus WT controls. In contrast, Adipo-KO mice exhibited ~62% decreased induction of FABP4 responses to lipolysis, while Endo-KO mice showed only mildly decreased induction, indicating that adipocytes are the main source of increases in FABP4 during lipolysis. We did not detect any myeloid contribution to circulating FABP4. Surprisingly, despite the nearly intact induction of FABP4, 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. |
