Integrative metabolic regulation of peripheral tissue fatty acid oxidation by the SRC kinase family member Fyn.
Mice null for Fyn (a member of the Src family of nonreceptor tyrosine kinases) display a reduced percentage of adipose mass associated with decreased adipocyte cell size. In parallel, there is a substantial reduction in fasting plasma glucose, insulin, triglycerides, and free fatty acids concomitant with decreased intrahepatocellular and intramyocellular lipid accumulation. Importantly, the Fyn null mice exhibit improved glucose tolerance resulting from increased peripheral tissue (adipose and skeletal muscle) insulin sensitivity with a very small effect in the liver. Moreover, whole-body, adipose, and skeletal muscle fatty acid uptake and oxidation are increased along with AMP kinase activation and acetyl-CoA carboxylase inhibition. Together, these data demonstrate crosstalk between Src-family kinase activity and fatty acid oxidation and show that the loss of Fyn markedly improves peripheral tissue insulin sensitivity by relieving a selective negative modulation of AMP kinase activity in adipose tissue and skeletal muscle.
Bastie
Claire C
CC
Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794, USA.
Zong
Haihong
H
Xu
Jun
J
Busa
Bhavin
B
Judex
Stefan
S
Kurland
Irwin J
IJ
Pessin
Jeffrey E
JE
D000263:Adenylate Kinase / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002153:Calorimetry, Indirect; D005227:Fatty Acids / Q000378:metabolism*; D005947:Glucose; D007328:Insulin / Q000378:metabolism*; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism*; D010084:Oxidation-Reduction; D051076:Proto-Oncogene Proteins c-fyn / Q000235:genetics / Q000378:metabolism*; D014057:Tomography, X-Ray Computed
D005227:Fatty Acids; D007328:Insulin; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn; D000263:Adenylate Kinase; D005947:Glucose