Oleic Acid in the Ventral Tegmental Area Inhibits Feeding, Food Reward, and Dopamine Tone.
Neuropsychopharmacol.. 2017-08-31; 43(3): 607-616
DOI: 10.1038/npp.2017.203
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Hryhorczuk C(1)(2), Sheng Z(3), Décarie-Spain L(1)(4), Giguère N(5), Ducrot C(5), Trudeau LÉ(5), Routh VH(3), Alquier T(1)(6), Fulton S(1)(7).
Author information:
(1)CRCHUM and Montreal Diabetes Research Center, Montréal, QC, Canada.
(2)Department of Physiology, Université de Montréal, Montréal, QC, Canada.
(3)Rutgers New Jersey Medical School, Department of Pharmacology, Physiology and
Neuroscience, Rutgers University, Newark, NJ, USA.
(4)Department of Neurosciences, Université de Montréal, Montréal, QC, Canada.
(5)Department of Pharmacology, Université de Montréal, Montréal, QC, Canada.
(6)Department of Medicine, Université de Montréal, Montréal, QC, Canada.
(7)Department of Nutrition, Université de Montréal, Montréal, QC, Canada.
Long-chain fatty acids (FAs) act centrally to decrease food intake and hepatic
glucose production and alter hypothalamic neuronal activity in a manner that
depends on FA type and cellular transport proteins. However, it is not known
whether FAs are sensed by ventral tegmental area (VTA) dopamine (DA) neurons to
control food-motivated behavior and DA neurotransmission. We investigated the
impact of the monounsaturated FA oleate in the VTA on feeding, locomotion, food
reward, and DA neuronal activity and DA neuron expression of FA-handling proteins
and FA uptake. A single intra-VTA injection of oleate, but not of the saturated
FA palmitate, decreased food intake and increased locomotor activity.
Furthermore, intra-VTA oleate blunted the rewarding effects of high-fat/sugar
food in an operant task and inhibited DA neuronal firing. Using sorted DA neuron
preparations from TH-eGFP mice we found that DA neurons express FA transporter
and binding proteins, and are capable of intracellular transport of long-chain
FA. Finally, we demonstrate that a transporter blocker attenuates FA uptake into
DA neurons and blocks the effects of intra-VTA oleate to decrease food-seeking
and DA neuronal activity. Together, these results suggest that DA neurons detect
FA and that oleate has actions in the VTA to suppress DA neuronal activity and
food seeking following cellular incorporation. These findings highlight the
capacity of DA neurons to act as metabolic sensors by responding not only to
hormones but also to FA nutrient signals to modulate food-directed behavior.