The Effects of Weight Cycling on Central Reward Signalling

Abstract

The increased prevalence of obesity in our society is a cause for serious concern. Although lifestyle and diet changes are successful ways to lose weight, a high percentage of people weight cycle, also known as “yoyo” dieting. Evidence suggests weight cycling is no more detrimental to a person’s health than remaining obese, but there still remains speculation over the mechanisms involved in weight regain. One such model proposes the “food addiction” model, whereby a deficit in reward function can lead to a blunted reward response to eating, leading to over consumption. In this thesis, I aim to clarify the role of mesolimbic dopamine signalling. Firstly, a short, medium and chronic high fat (HF) feeding study was used to assess the development of changes in dopamine signalling. Secondly, to assess the effects of a single weight cycle on dopamine signalling, mice were fed control or HF diets, and swapped diet every 6 weeks. Finally, to assess the effect of rapid weight change, lean and DIO mice swapped to a HF diet or control diet for a week, respectively. Chronic HF diet increased dopamine-related gene expression and showed a similar expression profile as short term HF feeding. Medium term HF feeding on the other hand showed a decrease in dopamine related gene expression. Weight cycling appeared to have no clear uniform effect on dopamine-related gene expression. Rapid weight gain showed little change in dopamine-related gene expression in the reward areas. Conversely, rapid weight loss induced a decrease in tyrosine hydroxylase (TH) and dopamine receptor 2 (D2R) mRNA in the VTA, but with little change elsewhere. In conclusion, my data does not support the “food addiction” model of changes in dopamine signalling contributing to obesity. Similarly, there appears to be little effect on dopamine gene expression with rapid changes in body weight.