1. ¹Endocannabinoid Research Group, Institute of Biomolecular Chemistry National Research Council, Naples, Italy
2. ²Laboratoire de Biochimie et Génétique Moléculaire, Université de La Réunion, La Réunion, France
3. ³XI Divisione di Chirurgia Generale e dell'Obesità, Second University of Naples, Naples, Italy
4. ⁴Endocannabinoid Research Group, Department of Experimental Pharmacology, Università di Napoli 'Federico II', Naples, Italy
5. ⁵Department of Psychiatry, Second University of Naples, Naples, Italy

Correspondence: Dr V Di Marzo, Istituto di Chimica Biomolecolare-Endocannabinoid Research Group, Consiglio Nazionale delle Ricerche, Via Campi Flegrei 34, Comprensorio Olivetti, Fabbr 70, Pozzuoli, Napoli 80078, Italy. E-mail: vdimarzo@icmib.na.cnr.it

Received 5 June 2007; Revised 9 July 2007; Accepted 23 July 2007; Published online 20 August 2007.

Abstract

The endocannabinoid, arachidonoylethanolamide (AEA), and the peroxisome proliferator-activated receptor (PPAR)- ligand, oleylethanolamide (OEA) produce opposite effects on lipogenesis. The regulation of OEA and its anti-inflammatory congener, palmitoylethanolamide (PEA), in adipocytes and pancreatic -cells has not been investigated. We report here the results of studies on acylethanolamide regulation in these cells during obesity and hyperglycaemia, and provide an overview of acylethanolamide role in metabolic control. We analysed by liquid chromatography-mass spectrometry OEA and PEA levels in: 1) mouse 3T3F442A adipocytes during insulin-induced differentiation, 2) rat insulinoma RIN m5F -cells kept in 'low' or 'high' glucose, 3) adipose tissue and pancreas of mice with high fat diet-induced obesity (DIO), and 4) in visceral fat or blood of obese or type 2 diabetes (T2D) patients. In adipocytes, OEA levels remain unchanged during differentiation, whereas those of PEA decrease significantly, and are under the negative control of both leptin and PPAR-. PEA is significantly downregulated in subcutaneous adipose tissue of DIO mice. In RIN m5F insulinoma -cells, OEA and PEA levels are inhibited by 'very high' glucose, this effect being enhanced by insulin, whereas in cells kept for 24 h in 'high' glucose, they are stimulated by both glucose and insulin. Elevated OEA and PEA levels are found in the blood of T2D patients. Reduced PEA levels in hypertrophic adipocytes might play a role in obesity-related pro-inflammatory states. In -cells and human blood, OEA and PEA are down- or up-regulated under conditions of transient or chronic hyperglycaemia, respectively.