Endocannabinoids in adipocytes during differentiation and their role in glucose uptake.
The molecular basis for the control of energy balance by the endocannabinoid anandamide (AEA) is still unclear. Here, we show that murine 3T3-L1 fibroblasts have the machinery to bind, synthesize and degrade AEA, and that their differentiation into adipocytes increases by approximately twofold the binding efficiency of cannabinoid receptors (CBR), and by approximately twofold and approximately threefold, respectively, the catalytic efficiency of the AEA transporter and AEA hydrolase. In contrast, the activity of the AEA synthetase and the binding efficiency of vanilloid receptor were not affected by the differentiation process. In addition, we demonstrate that AEA increases by approximately twofold insulin-stimulated glucose uptake in differentiated adipocytes, according to a CB1R-dependent mechanism that involves nitric oxide synthase, but not lipoxygenase or cyclooxygenase. We also show that AEA binding to peroxisome proliferator-activated receptor-gamma, known to induce differentiation of 3T3-L1 fibroblasts into adipocytes, is not involved in the stimulation of glucose uptake.
Gasperi
V
V
Department of Biomedical Sciences, University of Teramo, Piazza A Moro 45, 64100, Teramo, Italy.
Fezza
F
F
Pasquariello
N
N
Bari
M
M
Oddi
S
S
Agrò
A Finazzi
AF
Maccarrone
M
M
D016475:3T3 Cells; D017667:Adipocytes / Q000378:metabolism* / Q000502:physiology; D000581:Amidohydrolases / Q000378:metabolism; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D015153:Blotting, Western; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D063388:Endocannabinoids; D004734:Energy Metabolism / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005947:Glucose / Q000378:metabolism*; D051379:Mice; D006899:Mixed Function Oxygenases / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D053284:Polyunsaturated Alkamides / Q000378:metabolism*; D043882:Receptors, Cannabinoid / Q000378:metabolism; D050916:TRPV Cation Channels / Q000378:metabolism; D000099252:Fatty Acid Amide Hydrolases
D000581:Amidohydrolases; D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D003577:Cytochrome P-450 Enzyme System; D063388:Endocannabinoids; D005947:Glucose; D006899:Mixed Function Oxygenases; D052247:Nitric Oxide Synthase Type II; D053284:Polyunsaturated Alkamides; D043882:Receptors, Cannabinoid; D050916:TRPV Cation Channels; D000099252:Fatty Acid Amide Hydrolases; C087226:arachidonoylethanolamide synthase; C078814:anandamide