Impaired Mitochondrial Fat Oxidation Induces FGF21 in Muscle

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2016 May 18

PMID 27184848

Citations 50

Authors

Bolormaa Vandanmagsar

Jaycob D Warfel

Shawna E Wicks

Sujoy Ghosh

J Michael Salbaum

David Burk

Olga S Dubuisson

Tamra M Mendoza

Jingying Zhang

Robert C Noland

Randall L Mynatt

Affiliations

Soon will be listed here.

Abstract

Fatty acids are the primary fuel source for skeletal muscle during most of our daily activities, and impaired fatty acid oxidation (FAO) is associated with insulin resistance. We have developed a mouse model of impaired FAO by deleting carnitine palmitoyltransferase-1b specifically in skeletal muscle (Cpt1b(m-/-)). Cpt1b(m-/-) mice have increased glucose utilization and are resistant to diet-induced obesity. Here, we show that inhibition of mitochondrial FAO induces FGF21 expression specifically in skeletal muscle. The induction of FGF21 in Cpt1b-deficient muscle is dependent on AMPK and Akt1 signaling but independent of the stress signaling pathways. FGF21 appears to act in a paracrine manner to increase glucose uptake under low insulin conditions, but it does not contribute to the resistance to diet-induced obesity.

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