Role and regulation of acylethanolamides in energy balance: focus on adipocytes and beta-cells

Br J Pharmacol. 2007 Nov;152(5):676-90. doi: 10.1038/sj.bjp.0707424. Epub 2007 Aug 20.


The endocannabinoid, arachidonoylethanolamide (AEA), and the peroxisome proliferator-activated receptor (PPAR)-alpha ligand, oleylethanolamide (OEA) produce opposite effects on lipogenesis. The regulation of OEA and its anti-inflammatory congener, palmitoylethanolamide (PEA), in adipocytes and pancreatic beta-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 beta-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-gamma. PEA is significantly downregulated in subcutaneous adipose tissue of DIO mice. In RIN m5F insulinoma beta-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 beta-cells and human blood, OEA and PEA are down- or up-regulated under conditions of transient or chronic hyperglycaemia, respectively.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Adipocytes / cytology
  • Adipocytes / drug effects
  • Adipocytes / metabolism*
  • Adult
  • Aged
  • Amides / blood
  • Amides / metabolism*
  • Animals
  • Arachidonic Acids / blood
  • Arachidonic Acids / metabolism
  • Diabetes Mellitus, Type 2 / blood
  • Endocannabinoids
  • Energy Metabolism / physiology*
  • Ethanolamines
  • Female
  • Humans
  • Insulin-Secreting Cells / cytology
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / metabolism*
  • Leptin / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • Models, Biological
  • Obesity / blood
  • Oleic Acids / blood
  • Oleic Acids / metabolism
  • PPAR gamma / agonists
  • PPAR gamma / genetics
  • PPAR gamma / metabolism
  • Palmitic Acids / blood
  • Palmitic Acids / metabolism
  • Polyunsaturated Alkamides / blood
  • Polyunsaturated Alkamides / metabolism
  • Review Literature as Topic
  • Structure-Activity Relationship


  • Amides
  • Arachidonic Acids
  • Endocannabinoids
  • Ethanolamines
  • Leptin
  • Oleic Acids
  • Oleylethanolamide
  • PPAR gamma
  • Palmitic Acids
  • Polyunsaturated Alkamides
  • palmidrol
  • anandamide