Impaired Mitochondrial Fat Oxidation Induces FGF21 in Muscle

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

doi:10.1016/j.celrep.2016.04.057

Cell Reports (May 2016)

Impaired Mitochondrial Fat Oxidation Induces FGF21 in Muscle

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

Bolormaa Vandanmagsar: Gene Nutrient Interactions Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808, USA
Jaycob D. Warfel: Gene Nutrient Interactions Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808, USA
Shawna E. Wicks: Gene Nutrient Interactions Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808, USA
Sujoy Ghosh: Computational Biology Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808, USA
J. Michael Salbaum: Genomics Core Facility, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808, USA
David Burk: Cell Biology and Bioimaging Core Facility, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808, USA
Olga S. Dubuisson: Gene Nutrient Interactions Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808, USA
Tamra M. Mendoza: Gene Nutrient Interactions Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808, USA
Jingying Zhang: Transgenic Core Facility, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808, USA
Robert C. Noland: Skeletal Muscle Metabolism Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808, USA
Randall L. Mynatt: Gene Nutrient Interactions Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808, USA

DOI: https://doi.org/10.1016/j.celrep.2016.04.057
Journal volume & issue: Vol. 15, no. 8
pp. 1686 – 1699

Abstract

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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 (Cpt1bm−/−). Cpt1bm−/− 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.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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