Anandamide increases the differentiation of rat adipocytes and causes PPARgamma and CB1 receptor upregulation

Obesity (Silver Spring). 2009 Oct;17(10):1830-8. doi: 10.1038/oby.2009.177. Epub 2009 Jun 18.

Abstract

Anandamide (N-arachidonoylethanolamine, AEA) or its metabolites participate in energy balance mainly through feeding modulation. In addition, AEA has been found to increase 3T3-L1 adipocyte differentiation process. In this study, the effect of AEA, R(+)-methanandamide (R(+)-mAEA), URB597, and indomethacin on primary rat adipocyte differentiation was evaluated by a flow cytometry method and by Oil Red-O staining. Reverse transcription-PCR and western blotting analysis were performed in order to study the effect of AEA on peroxisome proliferator-activated receptor (PPAR)gamma2, cannabinoid receptors (CBRs), fatty acid amidohydrolase (FAAH), and cyclooxygenase-2 (COX-2) expression, during the differentiation process. AEA increased adipocyte differentiation in primary cell cultures in a concentration- and time-dependent manner and induced PPARgamma2 gene expression, confirming findings with 3T3-L1 cell line. CB1R, FAAH, and COX-2 expression was also increased while CB2R expression was decreased. Inhibition of FAAH and COX-2 attenuated the AEA-induced differentiation. Our findings indicate that AEA regulates energy homeostasis not only by appetite modulation but may also regulate adipocyte differentiation and phenotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / cytology
  • Adipocytes / drug effects*
  • Adipocytes / enzymology
  • Adipocytes / metabolism
  • Adipose Tissue / cytology
  • Adipose Tissue / drug effects*
  • Adipose Tissue / enzymology
  • Adipose Tissue / metabolism
  • Amidohydrolases / biosynthesis
  • Amidohydrolases / genetics
  • Animals
  • Arachidonic Acids / pharmacology*
  • Benzamides / pharmacology
  • Blotting, Western
  • Carbamates / pharmacology
  • Cell Differentiation / drug effects*
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / physiology
  • Endocannabinoids
  • Enzyme Inhibitors / pharmacology
  • Flow Cytometry
  • Indomethacin / pharmacology
  • Male
  • PPAR gamma / biosynthesis*
  • PPAR gamma / genetics
  • Polyunsaturated Alkamides / pharmacology*
  • Rats
  • Rats, Wistar
  • Receptor, Cannabinoid, CB1 / biosynthesis*
  • Receptor, Cannabinoid, CB1 / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Up-Regulation / drug effects

Substances

  • Arachidonic Acids
  • Benzamides
  • Carbamates
  • Endocannabinoids
  • Enzyme Inhibitors
  • PPAR gamma
  • Polyunsaturated Alkamides
  • Receptor, Cannabinoid, CB1
  • cyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl ester
  • methanandamide
  • Cyclooxygenase 2
  • Amidohydrolases
  • fatty-acid amide hydrolase
  • anandamide
  • Indomethacin