A gut lipid messenger links excess dietary fat to dopamine deficiency.
Excessive intake of dietary fats leads to diminished brain dopaminergic function. It has been proposed that dopamine deficiency exacerbates obesity by provoking compensatory overfeeding as one way to restore reward sensitivity. However, the physiological mechanisms linking prolonged high-fat intake to dopamine deficiency remain elusive. We show that administering oleoylethanolamine, a gastrointestinal lipid messenger whose synthesis is suppressed after prolonged high-fat exposure, is sufficient to restore gut-stimulated dopamine release in high-fat-fed mice. Administering oleoylethanolamine to high-fat-fed mice also eliminated motivation deficits during flavorless intragastric feeding and increased oral intake of low-fat emulsions. Our findings suggest that high-fat-induced gastrointestinal dysfunctions play a key role in dopamine deficiency and that restoring gut-generated lipid signaling may increase the reward value of less palatable, yet healthier, foods.
The John B. Pierce Laboratory, New Haven, CT 06519, USA.
Luis A
LA
Tellez
Sara
S
Medina
Wenfei
W
Han
Jozelia G
JG
Ferreira
Paula
P
Licona-Limón
Xueying
X
Ren
Tukiet T
TT
Lam
Gary J
GJ
Schwartz
Ivan E
IE
de Araujo
D000818:Animals; D001066:Appetite; D003342:Corpus Striatum / Q000378:metabolism*; D004041:Dietary Fats / Q000008:administration & dosage*; D004298:Dopamine / Q000172:deficiency / Q000378:metabolism*; D063388:Endocannabinoids / Q000008:administration & dosage* / Q000096:biosynthesis / Q000502:physiology*; D002149:Energy Intake; D004983:Ethanolamines / Q000008:administration & dosage*; D005247:Feeding Behavior; D041981:Gastrointestinal Tract / Q000378:metabolism*; D006706:Homeostasis; D007421:Intestine, Small / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009829:Oleic Acids / Q000008:administration & dosage* / Q000096:biosynthesis / Q000502:physiology*; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism; D012201:Reward; D015398:Signal Transduction; D014630:Vagus Nerve / Q000502:physiology
D004041:Dietary Fats; D063388:Endocannabinoids; D004983:Ethanolamines; D009829:Oleic Acids; D047493:PPAR alpha; C033595:N-oleoylethanolamine; D004298:Dopamine