Conjugated Linoleic Acid (CLA) Stimulates Mitochondrial Biogenesis Signaling by the Upregulation of PPARγ Coactivator 1α (PGC‐1α) in C2C12 Cells

Abstract

Along with its effect on body fat reduction, dietary conjugated linoleic acid (CLA) has been reported to improve physical activity and endurance capacity in mice. It has been suggested these effects may in part be due to physiological changes in skeletal muscle, however, the mode of action is not completely understood. Thus, the purpose of this study was to determine the relevant mechanisms of CLA isomers for mitochondrial biogenesis, one of the most important adaptive responses in skeletal muscle. Both cis-9,trans-11 (c9,t11) and trans-10,cis-12 (t10,c12) CLA isomers increased the expression of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), however, only the t10,c12 isomer, but not c9,t11, increased phosphorylation of AMP-activated protein kinase (AMPK) compared to the control. Among downstream biomarkers of PGC-1α, the CLA mixed isomer enhanced the expression of peroxisome proliferator-activated receptor-δ (PPARδ). Both c9,t11 and t10,c12 CLA isomers increased expression of nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription factor A (Tfam), while the c9,t11 increased expression of cytochrome c (Cyt C) and t10,c12 CLA increased expression of voltage-dependent anion channel (VDAC), respectively. Both CLA isomers significantly increased mitochondrial DNA copy number compared to that of control. These findings suggest that the individual CLA isomers potentiate mitochondrial biogenesis via PGC-1α-NRF-1-Tfam signaling cascade, although downstream regulation may be isomer dependent.

Conjugated Linoleic Acid Regulates Body Composition and Locomotor Activity in a Sex‐Dependent Manner in Drosophila melanogaster

“…Similar to mammals, AMPKα is an important regulator of metabolic homeostasis in Drosophila (Johnson et al, ); thus, we determined if CLA influenced AMPKα activation as previously reported in C2C12 myotubes (Huang et al, ; Kim and Park, ). There were significant differences in AMPKα activity between sexes ( p < 0.0001) and diet ( p = 0.0384), with interaction between sex and diet ( p = 0.0048) (Fig.…”

Effects of Eicosapentaenoic Acid and Docosahexaenoic Acid on Mitochondrial DNA Replication and PGC-1α Gene Expression in C2C12Muscle Cells

“…This result indicates a link between the nucleus and mitochondria by directly regulating mtDNA replication and transcription (4–6). Previously it was reported that conjugated linoleic acid isomers up-regulated PGC-1α, NRF1, and Tfam expression in C 2 C 12 cells (27). Also, a recent study showed that ω-3 PUFA from cod fish oil induced the activation of PGC-1α and -β in rat skeletal muscles (28).…”

α-linolenic acid reduces TNF-induced apoptosis in C2C12 myoblasts by regulating expression of apoptotic proteins

“…Recently, 10t, 12c-conjugated linoleic acid has been also reported to stimulate mitochondrial biogenesis in C2C12 myoblasts. 19 These studies suggest that the cell biological response to different unsaturated fatty acids may depend from their different chemical structure (number and position of double bond and the presence or absence of a cis-9 double bond). In addition, the same fatty acid may have different actions on different cell type.…”