Regulation of fat intake in the absence of flavour signalling

• Published in: The Journal of physiology Vol. 590; no. 4; pp. 953 - 972
• Main Authors: Ferreira, Jozélia G., Tellez, Luis A., Ren, Xueying, Yeckel, Catherine W., de Araujo, Ivan E.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.02.2012; Wiley Subscription Services, Inc; Blackwell Science Inc
• Subjects: Animals; Basal Ganglia - physiology; Brain; Calories; Circuits; Cocaine; Dietary Fats; Digestive tract; Dopamine; Dopamine - physiology; Dopamine Antagonists - pharmacology; Dopamine receptors; Drug addiction; Energy intake; Energy Intake - physiology; Feeding Behavior - physiology; Flavor; Haloperidol; Haloperidol - pharmacology; Hunger; Male; Mice; Mice, Inbred C57BL; Neostriatum; Neuroscience: Behavioural/Systems/Cognitive; Nutrients; Receptors, Dopamine - physiology; Reinforcement; Stomach - physiology; Taste - physiology
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.2011.218289

Key points  •  The hedonic orosensory properties of fats strongly promote intake, but it remains unknown whether fat intake stimulates brain reward circuits in the absence of orosensory cues. •  We developed a behavioral assay that allows for the dissociation between orosensory versus post‐oral influences on fat intake. •  Mice trained to lick a dry spout to receive intra‐gastric infusions of fat emulsions maintained constant caloric intake in response to changes in energy density or hunger levels. •  Dopamine levels in dorsal and ventral striatum were responsive to gut infusions of fat emulsions, in such a way that (1) extracellular striatal dopamine levels fluctuate in proportion to the caloric density of nutrients infused in the gut; and (2) inhibiting dopamine receptor signalling disrupts the animals’ ability to maintain constant caloric intake across experimental sessions. •  Our results support the existence of a gut–brain dopamine axis that functions as a flavour‐independent central sensor of fat calories.   Animals, including humans, can achieve precise regulation of caloric intake by adjusting consumption in response to covert changes in energy density. It remains unknown, however, whether the presence of flavour cues are required for the ability to maintain constant caloric intake. Also unknown are the brain circuits that may function as the central calorie monitors that control adaptive adjustments in energy intake. Here we show that mice trained to lick a dry spout in order to receive intra‐gastric infusions of a fat emulsion maintained constant hourly caloric intake by adjusting the number of dry licks in response to changes in caloric density. Animals also increased dry licking according to hunger levels, and developed conditioned preferences for dry sippers associated with high calorie infusions. Importantly, striatal dopamine levels were closely associated with the amount of calories ingested, rather than with the number of dry licks produced. Dopamine levels in dorsal and ventral striatum also reflected caloric density in mice passively receiving intra‐gastric infusions of fat emulsions. Consistent with the above, systemic administration of the dopamine receptor blocker haloperidol markedly increased the production of dry licks needed to obtain high‐calorie infusions, as if the caloric density of the infusions had been diluted. Conversely, haloperidol markedly decreased the production of dry licks needed to obtain low‐calorie infusions. Taken together, our results support the proposition that brain dopamine circuits function as one central sensor of calorie ingestion, since (1) extracellular striatal dopamine levels fluctuate in proportion to the caloric density of nutrients infused in the gut; and (2) inhibiting dopamine receptor signalling disrupts the animals’ ability to maintain constant caloric intake across experimental sessions.