Rudnicki 2018 Elife

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Publications in the MiPMap
Rudnicki M, Abdifarkosh G, Nwadozi E, Ramos SV, Makki A, Sepa-Kishi DM, Ceddia RB, Perry CG, Roudier E, Haas TL (2018) Endothelial-specific FoxO1 depletion prevents obesity-related disorders by increasing vascular metabolism and growth. Elife 7:e39780.

» PMID: 30511639 Open Access

Rudnicki M, Abdifarkosh G, Nwadozi E, Ramos SV, Makki A, Sepa-Kishi DM, Ceddia RB, Perry CG, Roudier E, Haas TL (2018) Elife

Abstract: Impaired angiogenesis is a hallmark of metabolically dysfunctional adipose tissue in obesity. However, the underlying mechanisms restricting angiogenesis within this context remain ill-defined. Here, we demonstrate that induced endothelial-specific depletion of the transcription factor Forkhead Box O1 (FoxO1) in male mice led to increased vascular density in adipose tissue. Upon high-fat diet feeding, endothelial cell FoxO1-deficient mice exhibited even greater vascular remodeling in the visceral adipose depot, which was paralleled with a healthier adipose tissue expansion, higher glucose tolerance and lower fasting glycemia concomitant with enhanced lactate levels. Mechanistically, FoxO1 depletion increased endothelial proliferative and glycolytic capacities by upregulating the expression of glycolytic markers, which may account for the improvements at the tissue level ultimately impacting whole-body glucose metabolism. Altogether, these findings reveal the pivotal role of FoxO1 in controlling endothelial metabolic and angiogenic adaptations in response to high-fat diet and a contribution of the endothelium to whole-body energy homeostasis.

Keywords: FoxO1, Angiogenesis, Cell biology, Diet-induced obesity, Endothelial cells, Glycolysis, Human biology, Medicine, Mouse Bioblast editor: Plangger M O2k-Network Lab: CA Toronto Perry CG


Labels: MiParea: Respiration, nDNA;cell genetics, Genetic knockout;overexpression, Exercise physiology;nutrition;life style  Pathology: Obesity 

Organism: Mouse  Tissue;cell: Fat  Preparation: Intact cells 


Coupling state: OXPHOS  Pathway: N, NS  HRR: Oxygraph-2k 

Labels, 2018-12