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Cell Rep. 2016 May 24;15(8):1686-99. doi: 10.1016/j.celrep.2016.04.057. Epub 2016 May 12.

Impaired Mitochondrial Fat Oxidation Induces FGF21 in Muscle.

Author information

1
Gene Nutrient Interactions Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808, USA.
2
Computational Biology Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808, USA; Centre for Computational Biology and Program in Cardiovascular and Metabolic Disorders, Duke-NUS Graduate Medical School, Singapore 169857, Singapore.
3
Genomics Core Facility, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808, USA.
4
Cell Biology and Bioimaging Core Facility, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808, USA.
5
Transgenic Core Facility, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808, USA.
6
Skeletal Muscle Metabolism Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808, USA.
7
Gene Nutrient Interactions Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808, USA; Transgenic Core Facility, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808, USA. Electronic address: randall.mynatt@pbrc.edu.

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.

PMID:
27184848
PMCID:
PMC4880522
DOI:
10.1016/j.celrep.2016.04.057
[Indexed for MEDLINE]
Free PMC Article

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