The Gut-brain Axis in Food Reward and Alcohol Consumption

Overview

The aims of this project are to: 1. Determine if 3-weeks dietary supplementation with NOPE-EGCG (PhosphoLEANtm, 85mg NOPE+50mg EGCG per capsule) versus a placebo will improve performance on impulsivity, go/no-go tasks and negative outcome learning in heavy drinkers. 2. Evaluate whether supplementation with NOPE-EGCG versus placebo results in reductions in alcohol consumption. 3. Preliminary data in the rodent model suggests that rats treated with OEA shift preference for lower fat test stimuli. In aim 3 we will Determine if 3-weeks of supplementation with PhosphoLEAN shifts fat preference towards lower fat test puddings.

Similarities in striatocortical pathway dysfunction have been noted for alcoholism and obesity. In prior studies we have demonstrated an inverse relationship between body mass index and response in the dorsal striatum (DS) during consumption of a palatable milkshake\[1\]. We have also shown that the magnitude of the reduced response predicts weight gain, especially in individuals who carry a copy of the A1 allele of the taq1A polymorphism\[1\]. Since the A1 allele is associated with reduced striatal D2 receptors \[2-7\], this finding implicates the dopamine system in the reduced blood oxygen level dependent (BOLD) response. Our results also indicate that this reduced response is a consequence, rather than a cause of obesity, since gaining weight \[8\], but not risk for obesity \[9\] (by virtue of parental obesity), is associated with reduced DS response to palatable food. Taken together the results indicate that increased adiposity is associated with blunted DS response to palatable food that may reflect altered dopamine signaling. More recently we determined that reduced DS responses in overweight and obese subjects are associated with increased impulsivity measured with the BIS-11 and a go no/no-go task \[10\]. Heavy drinkers are also more likely to be impulsive \[11\]. In preliminary analyses of data on over 300 individuals assessed with the clinical core battery in the Center for the Translational Neuroscience of Alcoholism (CTNA), we found that higher scores on the BIS-11 and other measures of impulsivity were associated with greater alcohol consumption. Related to these findings in humans, preliminary work in rodents shows that exogenous administration of N-Acylethanolamines, such as oleoylethanolamine (OEA) can normalize high-fat diet induced dopamine decreases in DS. Human testing of OEA supplementation is possible based on the availability of a dietary supplement containing the OEA precursor NOPE-EGCG ((PhosphoLEANtm, 85mg NOPE+50mg EGCG per capsule). PhosphoLEAN has been shown to enhance adherence to dietary advice in overweight healthy subjects \[12-14\]. We therefore propose a pilot study to test whether PhosphoLEAN will improve performance on impulsivity, go/no-go tasks and negative outcome learning. Specifically, we will recruit heavy drinkers because they are more likely to be impulsive \[11\]. Phospholean may improve negative reinforcement learning in this population. This may lead to reductions in drinking as well. We will also explore whether the supplement leads to reductions in alcohol consumption and preference for high fat foods.