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Role of FoxO within the microvasculature of the skeletal muscle in diet‐induced obesity
Author(s) -
Roudier Emilie Annie,
Alim Karim,
Vu Vivian,
Liu Ying,
Birot Olivier,
Sweeney Gary
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.685.16
Subject(s) - foxo1 , skeletal muscle , endocrinology , medicine , adipose tissue , biology , chemistry , microbiology and biotechnology , protein kinase b , signal transduction
Obesity has emerged as a growing worldwide epidemic. Excessive accumulation of fat alters the adipose tissue as well as the peripheral tissues. In particular obesity induces capillary rarefaction in the skeletal muscle. We recently found that Forkhead box O1 (FoxO1) is an angiostatic factor in the endothelium of the skeletal muscle. Here we aim to study the role of endothelial FoxO1 during diet‐induced obesity (DIO). A significant reduction in capillary to fibre ratio and an increased expression of FoxO1 were observed in the skeletal muscle of high fat‐fed C57Bl6 mice (58% vs. 6% kCal fat for 14 weeks). By knocking‐down FoxO, we identified thrombospondin1, BMP and activin membrane‐bound inhibitor and soluble frizzled‐related protein 1 as FoxO targets in murine microvascular endothelial cells (EC). The expression of these genes also was altered in the muscles of the DIO mice, consistent with the increase in FoxO1 protein. To further study the role of FoxOs, DIO was induced in mice with EC‐directed deletion of FoxO1,3,4 proteins (ΔFoxO; MxCre+:FoxO1,3,4L/L). After 8 weeks, DIO induced a significant increase in weight gain in both wild‐type and ΔFoxO mice. After 14 weeks, we will characterize the metabolic alterations and the changes in the skeletal muscle microenvironment. Our work will determine the role that endothelial FoxO plays in promoting obesity‐induced capillary rarefaction.