Dietary triglycerides act on mesolimbic structures to regulate the rewarding and motivational aspects of feeding.

Publisher: Nature Publishing Group Specialist Journals Country of Publication: England NLM ID: 9607835 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5578 (Electronic) Linking ISSN: 13594184 NLM ISO Abbreviation: Mol Psychiatry Subsets: MEDLINE

Publication: 2000- : Houndmills, Basingstoke, UK : Nature Publishing Group Specialist Journals
Original Publication: Houndmills, Hampshire, UK ; New York, NY : Stockton Press, c1996-

Reward*; Brain/*metabolism ; Feeding Behavior/*physiology ; Motivation/*physiology ; Triglycerides/*blood; Amphetamine/pharmacology ; Animals ; Carotid Arteries/metabolism ; Central Nervous System Stimulants/pharmacology ; Lipoprotein Lipase/metabolism ; Male ; Mice, Inbred C57BL ; Motor Activity/drug effects ; Motor Activity/physiology

Circulating triglycerides (TGs) normally increase after a meal but are altered in pathophysiological conditions, such as obesity. Although TG metabolism in the brain remains poorly understood, several brain structures express enzymes that process TG-enriched particles, including mesolimbic structures. For this reason, and because consumption of high-fat diet alters dopamine signaling, we tested the hypothesis that TG might directly target mesolimbic reward circuits to control reward-seeking behaviors. We found that the delivery of small amounts of TG to the brain through the carotid artery rapidly reduced both spontaneous and amphetamine-induced locomotion, abolished preference for palatable food and reduced the motivation to engage in food-seeking behavior. Conversely, targeted disruption of the TG-hydrolyzing enzyme lipoprotein lipase specifically in the nucleus accumbens increased palatable food preference and food-seeking behavior. Finally, prolonged TG perfusion resulted in a return to normal palatable food preference despite continued locomotor suppression, suggesting that adaptive mechanisms occur. These findings reveal new mechanisms by which dietary fat may alter mesolimbic circuit function and reward seeking.

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K01 DA026504 United States DA NIDA NIH HHS; DA026504 United States DA NIDA NIH HHS

0 (Central Nervous System Stimulants)
0 (Triglycerides)
CK833KGX7E (Amphetamine)
EC 3.1.1.34 (Lipoprotein Lipase)

Date Created: 20140416 Date Completed: 20150806 Latest Revision: 20211021

20240104

PMC4303340

10.1038/mp.2014.31

24732670