Cited by 328Peroxisome Proliferator-Activated ReceptorsFatty Acid Research and HealthLipid metabolism and biosynthesis

Oleoylethanolamide Stimulates Lipolysis by Activating the Nuclear Receptor Peroxisome Proliferator-activated Receptor α (PPAR-α)

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Guzmán, Manuel, Lo Verme, Jesse, Fu, Jin, Oveisi, Fariba, Blázquez, Cristina, Piomelli, Daniele·2004·Journal of Biological Chemistry

Abstract

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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Crossref · 10.1074/jbc.m404087200

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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)”

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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
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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