Abstract
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.
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Acknowledgements
We thank Marie-Josée Bourque for neuron cultures and help with cell sorting, and Demetra Rodaros and Anna Kristyna Franco Flores for helping with intra-VTA surgeries and operant responding experiments. This work was supported by a CIHR grant (MOP123280) and New Investigator salary award to SF, by a CIHR grant (MOP115042) and Fonds de Recherche Québec-Santé salary award to TA, by CIHR (MOP106556) and Brain Canada/Krembil Foundation grants to L-ET, American Heart Association grants to VHR (14GRNT20380639 and 1RO1DK103676), and doctoral scholarships from the Montreal Diabetes Research Center/Université de Montréal and CMDO/Novo Nordisk to CH.
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Hryhorczuk, C., Sheng, Z., Décarie-Spain, L. et al. Oleic Acid in the Ventral Tegmental Area Inhibits Feeding, Food Reward, and Dopamine Tone. Neuropsychopharmacol. 43, 607–616 (2018). https://doi.org/10.1038/npp.2017.203
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DOI: https://doi.org/10.1038/npp.2017.203
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