Oleic acid stimulates complete oxidation of fatty acids through protein kinase A-dependent activation of SIRT1-PGC1α complex
Open accessAbstract
Fatty acids are essential components of the dynamic lipid metabolism in cells. Fatty acids can also signal to intracellular pathways to trigger a broad range of cellular responses. Oleic acid is an abundant monounsaturated omega-9 fatty acid that impinges on different biological processes, but the mechanisms of action are not completely understood. Here, we report that oleic acid stimulates the cAMP/protein kinase A pathway and activates the SIRT1-PGC1α transcriptional complex to modulate rates of fatty acid oxidation. In skeletal muscle cells, oleic acid treatment increased intracellular levels of cyclic adenosine monophosphate (cAMP) that turned on protein kinase A activity. This resulted in SIRT1 phosphorylation at Ser-434 and elevation of its catalytic deacetylase activity. A direct SIRT1 substrate is the transcriptional coactivator peroxisome proliferator-activated receptor γ coactivator 1-α (PGC1α), which became deacetylated and hyperactive after oleic acid treatment. Importantly, oleic acid, but not other long chain fatty acids such as palmitate, increased the expression of genes linked to fatty acid oxidation pathway in a SIRT1-PGC1α-dependent mechanism. As a result, oleic acid potently accelerated rates of complete fatty acid oxidation in skeletal muscle cells. These results illustrate how a single long chain fatty acid specifically controls lipid oxidation through a signaling/transcriptional pathway. Pharmacological manipulation of this lipid signaling pathway might provide therapeutic possibilities to treat metabolic diseases associated with lipid dysregulation. Background: Different fatty acids signal to control intracellular lipid dynamic metabolism. Results: In skeletal muscle cells, oleic acid induces cAMP/PKA and SIRT1 Ser-434 phosphorylation and activity, causing PGC1α deacetylation and increased fatty acid oxidation. Conclusion: Oleic acid signals to the SIRT1-PGC1α complex to increase rates of fatty acid oxidation. Significance: Pharmacological manipulation of the oleic acid signaling pathway might be a therapeutic option for conditions of lipid dysregulation.
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POo contains a high proportion of unsaturated fatty acids (54% MUFAs, 10% PUFAs), which have been reported to increase β-oxidation rates and reduce liver fat.
“POo contains a high proportion of unsaturated fatty acids (54% MUFAs, 10% PUFAs) (Table 1), which have been reported to increase β -oxidation rates (37, 39) and reduce liver fat (40).”
From Eucaloric diets enriched in palm olein, cocoa butter, and soybean oil did not differentially affect liver fat concentration in healthy participants: a 16-week randomized controlled trial. (2021) · cites this paper as [39]
The ‘Oleic Acid Increases Rates of Fatty Acid Oxidation’ section reports markedly increased oxidation after oleic acid treatment in skeletal muscle cells. This supports the β-oxidation portion for oleic acid, but not the broader implication that the unsaturated fatty acids in POo generally have this effect. The POo percentages are attributed to Table 1, and liver-fat reduction to citation 40, not to this source. (LLM, conf=0.86)
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- Authors
- Lim, J.-H., Gerhart-Hines, Z., Dominy, J. E., Lee, Y., Kim, S., Tabata, M., Xiang, Y. K., & Puigserver, P.
- Affiliations
- Harvard University (US)
- University of California, Davis (US)
- Corresponding author
- Puigserver, Pere
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2013-03
- Volume
- 288
- Issue
- 10
- Pages
- 7117-7126
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC3591621
- OpenAlex
- W2028600248
- Cited by
- 212
- References
- 40
- Citations by year
- 2026: 15 · 2025: 16 · 2024: 20 · 2023: 15 · 2022: 19 · 2021: 17 · 2020: 29 · 2019: 18 · 2018: 16 · 2017: 14 · 2016: 16 · 2015: 6 · 2014: 10 · 2013: 1
- FWCI
- 5.12
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, other-oa)
- Funders
- U.S. Department of Defense
- American Diabetes Association
- American Heart Association
- National Institutes of Health
- U.S. Public Health Service (R01 069966)
- National Heart, Lung, and Blood Institute (R01HL082846, R01-HL82846)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK069966)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- oleic acid, fatty acid oxidation, SIRT1, PGC-1α, protein kinase A, cAMP signaling, skeletal muscle, lipid signaling, fatty acid metabolism, metabolic disorders
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Acetylation, Animals, Cell Line, Cells, Cultured, Fatty Acids, Mice, Inbred C57BL, Mutation, Oxidation-Reduction, Phosphorylation, Serine, Transcription Factors, Blotting, Western, Transcriptional Activation, Trans-Activators, Cyclic AMP-Dependent Protein Kinases, Muscle, Skeletal, Oleic Acid, Reverse Transcriptase Polymerase Chain Reaction, Fluorescence Resonance Energy Transfer, RNA Interference, Multiprotein Complexes, Mice, Sirtuin 1
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