title: Impaired Mitochondrial Fat Oxidation Induces FGF21 in Muscle.
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.
authors.affiliation: Gene Nutrient Interactions Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808, USA.
authors.forename: Bolormaa
authors.initials: B
authors.lastname: Vandanmagsar
authors.affiliation: Gene Nutrient Interactions Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808, USA.
authors.forename: Jaycob D
authors.initials: JD
authors.lastname: Warfel
authors.affiliation: Gene Nutrient Interactions Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808, USA.
authors.forename: Shawna E
authors.initials: SE
authors.lastname: Wicks
authors.affiliation: 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.
authors.forename: Sujoy
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: Genomics Core Facility, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808, USA.
authors.forename: J Michael
authors.initials: JM
authors.lastname: Salbaum
authors.affiliation: Cell Biology and Bioimaging Core Facility, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808, USA.
authors.forename: David
authors.initials: D
authors.lastname: Burk
authors.affiliation: Gene Nutrient Interactions Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808, USA.
authors.forename: Olga S
authors.initials: OS
authors.lastname: Dubuisson
authors.affiliation: Gene Nutrient Interactions Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808, USA.
authors.forename: Tamra M
authors.initials: TM
authors.lastname: Mendoza
authors.affiliation: Transgenic Core Facility, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808, USA.
authors.forename: Jingying
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Skeletal Muscle Metabolism Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Noland
authors.affiliation: 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.
authors.forename: Randall L
authors.initials: RL
authors.lastname: Mynatt
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism; D052242:Adiponectin / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000378:metabolism; D052436:Adipose Tissue, White / Q000378:metabolism; D050154:Adiposity; D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D004734:Energy Metabolism; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D050356:Lipid Metabolism; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D009929:Organ Size; D010084:Oxidation-Reduction; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D013312:Stress, Physiological; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D052242:Adiponectin; D007328:Insulin; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors; D007334:Insulin-Like Growth Factor I; C558401:CPT1B protein, mouse; D002334:Carnitine O-Palmitoyltransferase; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D000263:Adenylate Kinase; D005947:Glucose