Identifying novel molecular mechanisms of ghrelin receptor signalling underlying neural control of food intake: interaction with stress and impulsivity

The gut-hormone, ghrelin, activates the centrally expressed growth hormone secretagogue 1a (GHS-R1a) receptor, or ghrelin receptor. The ghrelin receptor is a G-protein coupled receptor (GPCR) expressed in several brain regions, including the arcuate nucleus (Arc), lateral hypothalamus (LH), ventral tegmental area (VTA), nucleus accumbens (NAcc) and amygdala. Activation of the GHS-R1a mediates a multitude of biological activities, including release of growth hormone and food intake. The ghrelin signalling system also plays a key role in the hedonic aspects of food intake and activates the dopaminergic mesolimbic circuit involved in reward signalling. Recently, ghrelin has been shown to be involved in mediating a stress response and to mediate stress-induced food reward behaviour via its interaction with the HPA-axis at the level of the anterior pituitary. Here, we focus on the role of the GHS-R1a receptor in reward behaviour, including the motivation to eat, its anxiogenic effects, and its role in impulsive behaviour. We investigate the functional selectivity and pharmacology of GHS-R1a receptor ligands as well as crosstalk of the GHS-R1a receptor with the serotonin 2C (5-HT2C) receptor, which represent another major target in the regulation of eating behaviour, stress-sensitivity and impulse control disorders. We demonstrate, to our knowledge for the first time, the direct impact of GHS-R1a signalling on impulsive responding in a 2-choice serial reaction time task (2CSRTT) and show a role for the 5-HT2C receptor in modulating amphetamine-associated impulsive action. Finally, we investigate differential gene expression patterns in the mesocorticolimbic pathway, specifically in the NAcc and PFC, between innate low- and high-impulsive rats. Together, these findings are poised to have important implications in the development of novel treatment strategies to combat eating disorders, including obesity and binge eating disorders as well as impulse control disorders, including, substance abuse and addiction, attention deficit hyperactivity disorder (ADHD) and mood disorders.

Eating habits of a population undergoing a rapid dietary transition: portion sizes of traditional and non-traditional foods and beverages consumed by Inuit adults in Nunavut, Canada

Background: To determine the portion sizes of traditional and non-traditional foods being consumed by Inuit adults in three remote communities in Nunavut, Canada. Methods. A cross-sectional study was carried out between June and October, 2008. Trained field workers collected dietary data using a culturally appropriate, validated quantitative food frequency questionnaire (QFFQ) developed specifically for the study population. Results: Caribou, muktuk (whale blubber and skin) and Arctic char (salmon family), were the most commonly consumed traditional foods; mean portion sizes for traditional foods ranged from 10 g for fermented seal fat to 424 g for fried caribou. Fried bannock and white bread were consumed by >85% of participants; mean portion sizes for these foods were 189 g and 70 g, respectively. Sugar-sweetened beverages and energy-dense, nutrient-poor foods were also widely consumed. Mean portion sizes for regular pop and sweetened juices with added sugar were 663 g and 572 g, respectively. Mean portion sizes for potato chips, pilot biscuits, cakes, chocolate and cookies were 59 g, 59 g, 106 g, 59 g, and 46 g, respectively. Conclusions: The present study provides further evidence of the nutrition transition that is occurring among Inuit in the Canadian Arctic. It also highlights a number of foods and beverages that could be targeted in future nutritional intervention programs aimed at obesity and diet-related chronic disease prevention in these and other Inuit communities.