Palmitic acid follows a different metabolic pathway than oleic acid in human skeletal muscle cells; lower lipolysis rate despite an increased level of adipose triglyceride lipase.
Development of insulin resistance is positively associated with dietary saturated fatty acids and negatively associated with monounsaturated fatty acids. To clarify aspects of this difference we have compared the metabolism of oleic (OA, monounsaturated) and palmitic acids (PA, saturated) in human myotubes. Human myotubes were treated with 100μM OA or PA and the metabolism of [(14)C]-labeled fatty acid was studied. We observed that PA had a lower lipolysis rate than OA, despite a more than two-fold higher protein level of adipose triglyceride lipase after 24h incubation with PA. PA was less incorporated into triacylglycerol and more incorporated into phospholipids after 24h. Supporting this, incubation with compounds modifying lipolysis and reesterification pathways suggested a less influenced PA than OA metabolism. In addition, PA showed a lower accumulation than OA, though PA was oxidized to a relatively higher extent than OA. Gene set enrichment analysis revealed that 24h of PA treatment upregulated lipogenesis and fatty acid β-oxidation and downregulated oxidative phosphorylation compared to OA. The differences in lipid accumulation and lipolysis between OA and PA were eliminated in combination with eicosapentaenoic acid (polyunsaturated fatty acid). In conclusion, this study reveals that the two most abundant fatty acids in our diet are partitioned toward different metabolic pathways in muscle cells, and this may be relevant to understand the link between dietary fat and skeletal muscle insulin resistance.
Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Norway. s.s.bakke@farmasi.uio.no
Siril S
SS
Bakke
Cedric
C
Moro
Nataša
N
Nikolić
Nina P
NP
Hessvik
Pierre-Marie
PM
Badin
Line
L
Lauvhaug
Katarina
K
Fredriksson
Matthijs K C
MK
Hesselink
Mark V
MV
Boekschoten
Sander
S
Kersten
Michael
M
Gaster
G Hege
GH
Thoresen
Arild C
AC
Rustan
D000273:Adipose Tissue / Q000201:enzymology*; D000328:Adult; D002478:Cells, Cultured; D015118:Eicosapentaenoic Acid / Q000494:pharmacology; D005990:Glycerol / Q000378:metabolism; D006801:Humans; D008049:Lipase / Q000032:analysis*; D008066:Lipolysis; D053858:Metabolic Networks and Pathways; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D019301:Oleic Acid / Q000378:metabolism*; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation; D019308:Palmitic Acid / Q000378:metabolism*
D019301:Oleic Acid; D019308:Palmitic Acid; D015118:Eicosapentaenoic Acid; D008049:Lipase; D005990:Glycerol