Vav2 Catalysis-dependent Pathways Contribute to Skeletal Muscle Growth and Metabolic Homeostasis

Overview

Journal Nat Commun

Specialty Biology

Date 2020 Nov 17

PMID 33199701

Citations 16

Authors

Sonia Rodriguez-Fdez

L Francisco Lorenzo-Martin

Isabel Fernandez-Pisonero

Begona Porteiro

Christelle Veyrat-Durebex

Daniel Beiroa

Omar Al-Massadi

Antonio Abad

Carlos Dieguez

Roberto Coppari

Ruben Nogueiras

Xose R Bustelo

Affiliations

Soon will be listed here.

Abstract

Skeletal muscle promotes metabolic balance by regulating glucose uptake and the stimulation of multiple interorgan crosstalk. We show here that the catalytic activity of Vav2, a Rho GTPase activator, modulates the signaling output of the IGF1- and insulin-stimulated phosphatidylinositol 3-kinase pathway in that tissue. Consistent with this, mice bearing a Vav2 protein with decreased catalytic activity exhibit reduced muscle mass, lack of proper insulin responsiveness and, at much later times, a metabolic syndrome-like condition. Conversely, mice expressing a catalytically hyperactive Vav2 develop muscle hypertrophy and increased insulin responsiveness. Of note, while hypoactive Vav2 predisposes to, hyperactive Vav2 protects against high fat diet-induced metabolic imbalance. These data unveil a regulatory layer affecting the signaling output of insulin family factors in muscle.

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