DOI . ORG {
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Title[redir]:
Oleylethanolamide regulates feeding and body weight through activation of the nuclear receptor PPAR-α | Nature
Description:
Oleylethanolamide (OEA) is a naturally occurring lipid that regulates satiety and body weight1,2. Although structurally related to the endogenous cannabinoid anandamide, OEA does not bind to cannabinoid receptors and its molecular targets have not been defined. Here we show that OEA binds with high affinity to the peroxisome-proliferator-activated receptor-α (PPAR-α), a nuclear receptor that regulates several aspects of lipid metabolism. Administration of OEA produces satiety and reduces body weight gain in wild-type mice, but not in mice deficient in PPAR-α. Two distinct PPAR-α agonists have similar effects that are also contingent on PPAR-α expression, whereas potent and selective agonists for PPAR-γ and PPAR-β/δ are ineffective. In the small intestine of wild-type but not PPAR-α-null mice, OEA regulates the expression of several PPAR-α target genes: it initiates the transcription of proteins involved in lipid metabolism and represses inducible nitric oxide synthase, an enzyme that may contribute to feeding stimulation. Our results, which show that OEA induces satiety by activating PPAR-α, identify an unexpected role for this nuclear receptor in regulating behaviour, and raise possibilities for the treatment of eating disorders.
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Keywords {🔍}
article, google, scholar, cas, nature, receptor, access, pparα, peroxisome, lipid, proliferatoractivated, content, regulates, receptors, mice, expression, ads, fatty, supplementary, cookies, feeding, nuclear, piomelli, oea, usa, privacy, information, body, weight, open, ppars, sci, acid, california, data, gaetani, oveisi, rodríguez, fonseca, effects, nitric, oxide, pdf, obesity, gene, rat, proc, natl, acad, activators,
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nature portfolio permissions reprints privacy policy research peroxisome-proliferator-activated receptor-α advertising subscribe nature peroxisome proliferator-activated receptors rodríguez de fonseca ppar-α target genes social media clofibric acid-activated receptor nature 414 nature 425 nature author information authors jesse lo verme development acyl-coa synthetase genes olive oil-derived endocannabinoid author correspondence nuclear receptor ppar-α ppar-α-null mice naaa-regulated lipid signaling distinct ppar-α agonists personal data barbara di giacomo springerlink instant access data protection permissions ppar-β/δ oleylethanolamide regulates feeding ppar-α expression european economic area privacy activating ppar-α diet-induced obesity daniele piomelli antonia serrano db/db mice naturally occurring lipid explore content subscription content fatty acids activate polyunsaturated fatty acids article fu institutional subscriptions read diabetic chinese hamsters streptozotocin-diabetic rats obese zucker rats
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description:Oleylethanolamide (OEA) is a naturally occurring lipid that regulates satiety and body weight1,2. Although structurally related to the endogenous cannabinoid anandamide, OEA does not bind to cannabinoid receptors and its molecular targets have not been defined. Here we show that OEA binds with high affinity to the peroxisome-proliferator-activated receptor-α (PPAR-α), a nuclear receptor that regulates several aspects of lipid metabolism. Administration of OEA produces satiety and reduces body weight gain in wild-type mice, but not in mice deficient in PPAR-α. Two distinct PPAR-α agonists have similar effects that are also contingent on PPAR-α expression, whereas potent and selective agonists for PPAR-γ and PPAR-β/δ are ineffective. In the small intestine of wild-type but not PPAR-α-null mice, OEA regulates the expression of several PPAR-α target genes: it initiates the transcription of proteins involved in lipid metabolism and represses inducible nitric oxide synthase, an enzyme that may contribute to feeding stimulation. Our results, which show that OEA induces satiety by activating PPAR-α, identify an unexpected role for this nuclear receptor in regulating behaviour, and raise possibilities for the treatment of eating disorders.
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headline:Oleylethanolamide regulates feeding and body weight through activation of the nuclear receptor PPAR-α
description:Oleylethanolamide (OEA) is a naturally occurring lipid that regulates satiety and body weight1,2. Although structurally related to the endogenous cannabinoid anandamide, OEA does not bind to cannabinoid receptors and its molecular targets have not been defined. Here we show that OEA binds with high affinity to the peroxisome-proliferator-activated receptor-α (PPAR-α), a nuclear receptor that regulates several aspects of lipid metabolism. Administration of OEA produces satiety and reduces body weight gain in wild-type mice, but not in mice deficient in PPAR-α. Two distinct PPAR-α agonists have similar effects that are also contingent on PPAR-α expression, whereas potent and selective agonists for PPAR-γ and PPAR-β/δ are ineffective. In the small intestine of wild-type but not PPAR-α-null mice, OEA regulates the expression of several PPAR-α target genes: it initiates the transcription of proteins involved in lipid metabolism and represses inducible nitric oxide synthase, an enzyme that may contribute to feeding stimulation. Our results, which show that OEA induces satiety by activating PPAR-α, identify an unexpected role for this nuclear receptor in regulating behaviour, and raise possibilities for the treatment of eating disorders.
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