Regulation of food intake by oleoylethanolamide

Verme, Jesse Lo; Gaetani, Silvana; Fu, Jin; Oveisi, Fariba; Burton, Katherine J.; Piomelli, Daniele

doi:10.1007/s00018-004-4494-0

Cited by 153 publications

(134 citation statements)

References 79 publications

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“…The lack of information concerning effects on in vivo amino acid metabolism prompted the current study. Important metabolic effects of PPAR␣ agonists can potentially be mediated via reductions in food intake (22). In our experience, reduced food intake can occur in response to structurally unrelated agonists at high doses relative to those required for lipid lowering.…”

Section: Discussionmentioning

confidence: 92%

Beyond lipids, pharmacological PPARα activation has important effects on amino acid metabolism as studied in the rat

Sheikh

Camejo²,

Lanne³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

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nists have been characterized largely in terms of their effects on lipids and glucose metabolism, whereas little has been reported about effects on amino acid metabolism. We studied responses to the PPAR␣ agonist WY 14,643 (30 mol⅐ kg Ϫ1 ⅐ day Ϫ1 for 4 wk) in rats fed a saturated fat diet. Plasma and urine were analyzed with proton NMR. Plasma amino acids were measured using HPLC, and hepatic gene expression was assessed with DNA arrays. The high-fat diet elevated plasma levels of insulin and triglycerides (TG), and WY 14,643 treatment ameliorated this insulin resistance and dyslipidemia, lowering plasma insulin and TG levels. In addition, treatment decreased body weight gain, without altering cumulative food intake, and increased liver mass. WY 14,643 increased plasma levels of 12 of 22 amino acids, including glucogenic and some ketogenic amino acids, whereas arginine was significantly decreased. There was no alteration in branched-chain amino acid levels. Compared with the fat-fed control animals, WY 14,643-treated animals had raised plasma urea and ammonia levels as well as raised urine levels of N-methylnicotinamide and dimethylglycine. WY 14,643 induced changes in a number of key genes involved in amino acid metabolism in addition to expected effects on hepatic genes involved in lipid catabolism and ketone body formation. In conclusion, the present results suggest that, in rodents, effects of pharmacological PPAR␣ activation extend beyond control of lipid metabolism to include important effects on whole body amino acid mobilization and hepatic amino acid metabolism.peroxisome proliferator-activated receptor-␣ PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-␣ (PPAR␣) agonists are used clinically to treat dyslipidemia and to reduce the risk of cardiovascular complications (7). The beneficial effects of these agents appear to be most significant in patients with insulin resistance and diabetes (32). It is clear that a major and primary action of PPAR␣ activation is the transcriptional regulation of genes involved in lipid metabolism (36). However, the effects of PPAR␣ activation may not be limited to lipid metabolism, given the established interactions between the major substrate classes (19), e.g., the glucose-fatty acid cycle (29) and the glucose-alanine cycle (10). In terms of glucose metabolism, an important physiological role of PPAR␣ is suggested by the hypoglycemia in response to prolonged fasting developed by mice lacking PPAR␣ (17). Furthermore, treatment of fat-fed rats with the selective PPAR␣ agonist WY 14,643 resulted in increases in whole body and skeletal muscle insulin-stimulated glucose utilization, with the enhancement in muscle insulin sensitivity related to the degree of reduction in local lipid accumulation (39). Surprisingly little has been reported concerning effects of PPAR␣ activation on amino acid metabolism, although work based largely on analysis of mRNA in mouse liver (23) suggests an important influence on the handling of this substrate class.The aim of the present study was to provide...

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Section: Discussionmentioning

confidence: 92%

Beyond lipids, pharmacological PPARα activation has important effects on amino acid metabolism as studied in the rat

Sheikh

Camejo²,

Lanne³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

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“…An alternative target to treat inflammation is to block fatty acid amide hydrolase (Cravatt et al, 1996), the enzyme that is predominantly responsible for the biodegradation of the endogenous cannabinoid N-arachidonoyl ethanolamine or anandamide (Devane et al, 1992), as well as other fatty acid amides (FAAs) including the analgesic/antiinflammatory compound N-palmitoyl ethanolamine (Lo Verme et al, 2005a), the appetite modulating ligand N-oleoyl ethanolamine (Lo Verme et al, 2005b), and the sleepinducing agent oleamide (Basile et al, 1999;Cravatt et al, 1996). Direct support that FAAH has a key role in regulating the activities of exogenous and endogenous FAAs was revealed in FAAH (-/-) mice (Cravatt et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of fatty acid amides in the carrageenan-induced paw edema model

et al. 2008

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While it has long been recognized that Δ 9 -tetrahydrocannabinol (THC), the primary psychoactive constituent of cannabis, and other cannabinoid receptor agonists possess anti-inflammatory properties, their well known CNS effects have dampened enthusiasm for therapeutic development. On the other hand, genetic deletion of fatty acid amide hydrolase (FAAH), the enzyme responsible for degradation of fatty acid amides, including endogenous cannabinoid N-arachidonoyl ethanolamine (anandamide; AEA), N-palmitoyl ethanolamine (PEA), N-oleoyl ethanolamine (OEA), and oleamide, also elicits anti-edema, but does not produce any apparent cannabinoid effects. The purpose of the present study was to investigate whether exogenous administration of FAAs would augment the anti-inflammatory phenotype of FAAH (-/-) mice in the carrageenan model. Thus, we evaluated the effects of the FAAs AEA, PEA, OEA, and oleamide in wild-type and FAAH (-/-) mice. For comparison, we evaluated the anti-edema effects of THC, dexamethasone (DEX), a synthetic glucocorticoid, diclofenac (DIC), a nonselective cyclooxygenase (COX) inhibitor, in both genotypes. A final study determined if tolerance to the anti-edema effects of PEA occurs after repeated dosing. PEA, THC, DEX, DIC elicited significant decreases in carrageenan-induced paw edema in wild type mice. In contrast OEA produced a less reliable anti-edema effect than these other drugs, and AEA and oleamide failed to produce any significant decreases in paw edema. Moreover, none of the agents evaluated augmented the anti-edema phenotype of FAAH (-/-) mice, suggesting that maximal antiedema effects had already been established. PEA was the most effective FAA in preventing paw edema and its effects did not undergo tolerance. While the present findings do not support a role for AEA in preventing carrageenan-induced edema, PEA administration and FAAH blockade elicited anti-edema effects of an equivalent magnitude as produced by THC, DEX, and DIC in this assay.

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“…The former has both anti-inflammatory and antinociceptive properties (Calignano, 1998); it does not bind to cannabinoid receptors (Showalter et al, 1996) although its effects are antagonised by cannabinoid CB 2 antagonists (Calignano et al, 1998). The latter is a naturally occurring lipid that regulates feeding and body weight (Fu et al, 2003;Lo Verme et al, 2005b).…”

Section: Introductionmentioning

confidence: 99%

Synergistic antinociceptive effects of anandamide, an endocannabinoid, and nonsteroidal anti-inflammatory drugs in peripheral tissue: A role for endogenous fatty-acid ethanolamides?

Guindon

LoVerme

Léan

et al. 2006

European Journal of Pharmacology

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Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit fatty-acid amide hydrolase (FAAH), the enzyme responsible for the metabolism of anandamide, an endocannabinoid. It has been suggested that the mechanisms of action of NSAIDs could be due to inhibition of cyclooxygenase (COX) and also to an increase in endocannabinoid concentrations. In a previous study we have demonstrated that the local analgesic interaction between anandamide and ibuprofen (a non-specific COX inhibitor) was synergistic for the acute and inflammatory phases of the formalin test. To test this hypothesis further, we repeated similar experiments with rofecoxib (a selective COX-2 inhibitor) and also measured the local concentrations of anandamide, and of two fatty-acid amides, oleoylethanolamide and palmitoylethanolamide. We established the ED 50 for anandamide (34.52 pmol ± 17.26) and rofecoxib (381.72 pmol ± 190.86) and showed that the analgesic effect of the combination was synergistic. We also found that paw tissue levels of anandamide, oleoylethanolamide and palmitoylethanolamide were significantly higher when anandamide was combined with NSAIDs and that this effect was greater with rofecoxib. In conclusion, local injection of anandamide or rofecoxib was antinociceptive in a test of acute and inflammatory pain and the combination of anandamide with rofecoxib was synergistic. Finally, locally injected anandamide with either NSAID (ibuprofen or rofecoxib) generates higher amount of fatty-acid ethanolamides. The exact comprehension of the mechanisms involved needs further investigation.

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Regulation of food intake by oleoylethanolamide

Cited by 153 publications

References 79 publications

Beyond lipids, pharmacological PPARα activation has important effects on amino acid metabolism as studied in the rat

Beyond lipids, pharmacological PPARα activation has important effects on amino acid metabolism as studied in the rat

Evaluation of fatty acid amides in the carrageenan-induced paw edema model

Synergistic antinociceptive effects of anandamide, an endocannabinoid, and nonsteroidal anti-inflammatory drugs in peripheral tissue: A role for endogenous fatty-acid ethanolamides?

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