Trans-10, cis-12 conjugated linoleic acid inhibits skeletal muscle differentiation and GLUT4 expression independently from NF-κB activation.
METHODS
The capacity of skeletal muscle to contribute to glucose homeostasis depends on muscular insulin sensitivity. The expression of glucose transporter (GLUT)-4 is increased during myoblast differentiation, a process essential in maintenance of adult muscle. Therefore, processes that affect muscle differentiation may influence insulin dependent glucose homeostasis. Conjugated linoleic acids, and in particular trans-10, cis-12 CLA (t10, c12-CLA), are potent inducers of NF-kB in cultured skeletal myotubes, and NF-kB activation inhibits muscle differentiation. The aims of this study were to evaluate whether CLAs inhibit myogenic differentiation and lower GLUT4 mRNA expression and to address the involvement of NF-kB activation in potential effects of CLA on these processes.


RESULTS
Incubation of C2C12 cells with t10, c12-CLA blocked the formation of myotubes, which was accompanied by reduced expression of the muscle specific genes creatine kinase, myogenin, myosin heavy chain perinatal and myosin heavy chain IIB, as well as decreased GLUT4 mRNA levels. However, genetic blockade of NF-kB was not sufficient to restore reduced myosin heavy chain protein expression following t10, c12-CLA treatment. Surprisingly, in contrast to myotubes, t10, c12-CLA was not able to activate NF-kB transcriptional activity in myoblasts.


CONCLUSIONS
In conclusion, t10, c12-CLA inhibits myogenic differentiation and GLUT4 expression, independently from NF-kB activation.
Hommelberg
Pascal P H
PP
Department of Human Biology, Maastricht University Medical Centre+, Maastricht, The Netherlands.
Plat
Jogchum
J
Remels
Alexander H V
AH
van Essen
Anon L M
AL
Kelders
Marco C J M
MC
Mensink
Ronald P
RP
Schols
Annemie M W J
AM
Langen
Ramon C J
RC
D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D005786:Gene Expression Regulation; D051275:Glucose Transporter Type 4 / Q000235:genetics* / Q000378:metabolism; D007333:Insulin Resistance; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D051379:Mice; D024510:Muscle Development; D018485:Muscle Fibers, Skeletal / Q000166:cytology*; D032446:Myoblasts / Q000166:cytology; D018995:Myosin Heavy Chains / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D051381:Rats
D051275:Glucose Transporter Type 4; D044243:Linoleic Acids, Conjugated; D016328:NF-kappa B; C495693:Slc2a4 protein, mouse; C496197:trans-10,cis-12-conjugated linoleic acid; D018995:Myosin Heavy Chains