Vascular endothelial growth factor B promotes transendothelial fatty acid transport into skeletal muscle via histone modifications during catch-up growth.

Vascular endothelial growth factor B promotes transendothelial fatty acid transport into skeletal muscle via histone modifications during catch-up growth.
Am J Physiol Endocrinol Metab. 2020 Sep 21;:
Authors: Lu X, Hu S, Liao Y, Zheng J, Zeng T, Zhong X, Liu G, Chen L, Chen L
Abstract
Caloric restriction (CR) followed by refeeding, a phenomenon known as catch-up growth (CUG), results in excessive lipid deposition and insulin resistance in skeletal muscle, but the underlying mechanisms remain elusive. Recent reports have suggested that vascular endothelial growth factor B (VEGF-B) controls muscle lipid accumulation by regulating endothelial fatty acid transport. Here, we found continuous activation of VEGF-B signaling and increased lipid uptake in skeletal muscle from CR to refeeding, as well as increased lipid deposition and impaired insulin sensitivity after refeeding in the skeletal muscle of CUG rodents. Inhibiting VEGF-B signaling ameliorated fatty acid uptake in and transport across endothelial cells. Knockdown of Vegfb in the tibialis anterior (TA) muscle of CUG mice significantly attenuated muscle lipid accumulation and improved muscle insulin signaling by decreasing lipid uptake. Furthermore, we showed that aberrant histone methylation (H3K9me1) and acetylation (H3K14ac and H3K18ac) at the Vegfb promoter might be the main cause of persistent VEGF-B up-regulation in skeletal muscle during CUG. Modifying these aberrant loci usi...

Source: Am J Physiol Endocri... - September 20, 2020 Category: Endocrinology Authors: Lu X, Hu S, Liao Y, Zheng J, Zeng T, Zhong X, Liu G, Chen L, Chen L Tags: Am J Physiol Endocrinol Metab Source Type: research