High-fat feeding can cause impairments in the functioning of the mesolimbic dopamine system, says Stephanie Fulton of the University of Montreal and the CHUM Research Centre (CRCHUM.) This system is a critical brain pathway controlling motivation. Fulton’s findings, published today in Neuropsychopharmacology, may have great health implications. “Our research shows that independent of weight gain and obesity, high-fat feeding can cause impairments in the functioning of the brain circuitry profoundly implicated in mood disorders, drug addiction, and overeating – several states and pathologies that impinge on motivation and hedonia,” Fulton explained. Hedonia relates to a mental state of wellbeing. “Another key finding is that the effects of prolonged high-fat feeding to dampen the sensitivity of this brain reward system are specific to saturated fats – palm oil used in this study – but not monounsaturated fat such as the olive oil used in this study.”
The research team obtained these findings by working with three groups of rats. The first group of rats was the control group: they were given a low-fat diet containing roughly equal amounts of monounsaturated and saturated fatty acids. The second group was given a monounsaturated high fat diet, of which 50% of the calories were from fat derived from olive oil. The third group was given a saturated high fat diet – again, 50% of the calories were from fat, but this time derived from palm oil. The high-fat diets were all the same in terms of sugars, proteins, fat content and caloric density, and the animals were free to eat as much or as little as they liked. After eight weeks, all of the rats still had comparable body weights and levels of insulin, leptin (which are major metabolic hormones) and relative glycemia.
At this time, the rats underwent a series of behavioural and biochemical tests known to be indicative of the functioning of rats’ dopamine system. “We established that the rats on the palm diet had a significantly blunted dopamine function,” said Cecile Hryhorczuk, the first author of the study. “Our research group and others hypothesize that this leads the brain to try to compensate by heightening reward-seeking behaviour, much like the phenomenon of drug tolerance where one has to increase the drug dose over time to get the same high. So, a person consuming too much saturated fat may then compensate a reduced reward experience by seeking out and consuming more high-fat and high-sugar foods to get the same level of pleasure or reward.”
Fulton’s study is the first of its kind to show that, regardless of weight changes, unrestrained intake of saturated fats can have negative effects on the controls of motivation by the brain. “As we were able to control for changes in body weight, hormones and glucose levels, we think that the fats may be affecting the dopamine system by a direct action in the brain,” Fulton said. “We in fact have separate evidence that brain inflammation could be involved in this process, as it is evoked by saturated high-fat feeding, which will be presented in a future publication.”
Stephanie Fulton and her colleagues published “Dampened mesolimbic dopamine function and signaling by saturated but not monounsaturated dietary lipids” in Neuropsychopharmacology on July 14, 2015. Stephanie Fulton, PhD, is a professor at the University of Montreal’s Department of Nutrition while Cecile Hryhorczuk, MSc, is affiliated with the university’s Department of Physiology. Both are researchers at the Montreal Diabetes Centre and the CHUM Research Centre (CRCHUM.)
Funding: This research was supported by funding from the Canadian Institutes for Health Research (MOP123280, MOP115042, MOP9575), the Fonds de Recherche Quebec-Santé, the National Science and Engineering Research Council (249848-2007 RGPIN), the Montreal Diabetes Research Center/Université de Montréal and CMDO/Novo Nordisk.
Source: William Raillant-Clark – University of Montreal
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Original Research: Abstract for “Dampened mesolimbic dopamine function and signaling by saturated but not monounsaturated dietary lipids” by Cecile Hryhorczuk, Marc Florea, Demetra Rodaros, Isabelle Poirier, Caroline Daneault, Christine Des Rosiers, Andreas Arvanitogiannis, Thierry Alquier and Stephanie Fulton in Neuropsychopharmacology. Published online July 14 2015 doi:10.1038/npp.2015.207
Dampened mesolimbic dopamine function and signaling by saturated but not monounsaturated dietary lipids
Over consumption of dietary fat is increasingly linked with motivational and emotional impairments. Human and animal studies demonstrate associations between obesity and blunted reward function at the behavioral and neural level, but it is unclear to what degree such changes are a consequence of an obese state and whether they are contingent on dietary lipid class. We sought to determine the impact of prolonged ad libitum intake of diets rich in saturated or monounsaturated fat, separate from metabolic signals associated with increased adiposity, on dopamine (DA)-dependent behaviors and to identify pertinent signaling changes in the nucleus accumbens (NAc). Male rats fed a saturated (palm oil), but not an isocaloric monounsaturated (olive oil), high-fat diet exhibited decreased sensitivity to the rewarding (place preference) and locomotor-sensitizing effects of amphetamine as compared to low-fat diet controls. Blunted amphetamine action by saturated high-fat feeding was entirely independent of caloric intake, weight gain and plasma levels of leptin, insulin and glucose and was accompanied by biochemical and behavioral evidence of reduced D1R signaling in the NAc. Saturated high-fat feeding was also tied to protein markers of increased AMPA receptor mediated plasticity and decreased DA transporter expression in the NAc but not to alterations in DA turnover and biosynthesis. Collectively, the results suggest that intake of saturated lipids can suppress DA signaling apart from increases in body weight and adiposity-related signals known to affect mesolimbic DA function, in part by diminishing D1 receptor signaling, and that equivalent intake of monounsaturated dietary fat protects against such changes.
“Dampened mesolimbic dopamine function and signaling by saturated but not monounsaturated dietary lipids” by Cecile Hryhorczuk, Marc Florea, Demetra Rodaros, Isabelle Poirier, Caroline Daneault, Christine Des Rosiers, Andreas Arvanitogiannis, Thierry Alquier and Stephanie Fulton in Neuropsychopharmacology. Published online July 14 2015 doi:10.1038/npp.2015.207