Oleoylethanolamide Stimulates Lipolysis by Activating the Nuclear Receptor Peroxisome Proliferator-activated Receptor α (PPAR-α)
Open accessAbstract
Amides of fatty acids with ethanolamine (FAE) are biologically active lipids that participate in a variety of biological functions, including the regulation of feeding. The polyunsaturated FAE anandamide (arachidonoylethanolamide) increases food intake by activating G protein-coupled cannabinoid receptors. On the other hand, the monounsaturated FAE oleoylethanolamide (OEA) reduces feeding and body weight gain by activating the nuclear receptor PPAR-alpha (peroxisome proliferator-activated receptor alpha). In the present report, we examined whether OEA can also influence energy utilization. OEA (1-20 microm) stimulated glycerol and fatty acid release from freshly dissociated rat adipocytes in a concentration-dependent and structurally selective manner. Under the same conditions, OEA had no effect on glucose uptake or oxidation. OEA enhanced fatty acid oxidation in skeletal muscle strips, dissociated hepatocytes, and primary cardiomyocyte cultures. Administration of OEA in vivo (5 mg kg(-1), intraperitoneally) produced lipolysis in both rats and wild-type mice, but not in mice in which PPAR-alpha had been deleted by homologous recombination (PPAR-alpha(-/-)). Likewise, OEA was unable to enhance lipolysis in adipocytes or stimulate fatty acid oxidation in skeletal muscle strips isolated from PPAR-alpha mice. The synthetic PPAR-alpha agonist Wy-14643 produced similar effects, which also were dependent on the presence of PPAR-alpha. Subchronic treatment with OEA reduced body weight gain and triacylglycerol content in liver and adipose tissue of diet-induced obese rats and wild-type mice, but not in obese PPAR-alpha(-/-) mice. The results suggest that OEA stimulates fat utilization through activation of PPAR-alpha and that this effect may contribute to its anti-obesity actions.
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OEA activates PPAR-alpha, a major regulator of lipid metabolism activated to induce a metabolic adaptive response to prolonged fasting.
“Since OEA has been shown to activate peroxisome proliferator-activated receptor alpha (PPAR-alpha) (Guzmán et al., 2004), a major regulator of lipid metabolism that is activated to induce a metabolic adaptive response to prolonged fasting (Kersten et al., 1999)”
From Sleep restriction alters plasma endocannabinoids concentrations before but not after exercise in humans (2016) · cites this paper as Guzmán et al., 2004
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- Authors
- Guzmán, M., Lo Verme, J., Fu, J., Oveisi, F., Blázquez, C., & Piomelli, D.
- Affiliations
- Universidad Complutense de Madrid (ES)
- University of California, Irvine (US)
- Corresponding author
- Piomelli, Daniele
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2004-07
- Volume
- 279
- Issue
- 27
- Pages
- 27849-27854
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2080373548
- Cited by
- 328
- References
- 37
- Citations by year
- 2026: 8 · 2025: 12 · 2024: 15 · 2023: 13 · 2022: 10 · 2021: 18 · 2020: 17 · 2019: 18 · 2018: 17 · 2017: 19 · 2016: 19 · 2015: 10 · 2014: 20 · 2013: 11 · 2012: 8
- FWCI
- 5.53
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- oleoylethanolamide, PPARα, lipolysis, fatty acid oxidation, energy metabolism, anti-obesity, diet-induced obesity, adipocytes, skeletal muscle, hepatocytes, cardiomyocytes, PPARα knockout mice, Wy-14,643, triglycerides, weight gain
- MeSH terms
- Adipose Tissue, Animals, Body Weight, Cell Nucleus, Cells, Cultured, Dose-Response Relationship, Drug, Fatty Acids, Glucose, Glycerol, Ligands, Lipolysis, Liver, Male, Mice, Inbred C57BL, Mice, Transgenic, Oleic Acids, Oxygen, Pyrimidines, Time Factors, Transcription Factors, Polymerase Chain Reaction, Rats, Wistar, Receptors, Cytoplasmic and Nuclear, Hepatocytes, Lipid Metabolism, Mice, Rats, Endocannabinoids
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