Nutritional, hormonal and genetic factors in the development of overeating tendency toward food addiction

Overeating is believed to be the primary factor responsible for the increasing prevalence of human obesity. A proportion of people develops a chronic obsessive/compulsive relationship to foods that is defined as food addiction (FA). The degree that FA contributes to obesity in the general population, and the key factors involved in FA, are unknown. The aims of the thesis were to assess and to find: 1) The prevalence of FA in the general population; 2) If clinical symptom counts of FA were significantly correlated with body composition measurements; 3) If food addicts were significantly more obese than controls, 4) If any macronutrient intake is associated with FA, 5) The link of hormones and neuropeptides that regulate appetite and metabolism with FA, 6) The differences of dietary nutrient intakes (micro- and macro-nutrients) between obese individuals with FA (FAO) or without FA (NFO), and 7) Discovery of novel FA associated candidate genes. The current thesis consists of three phases. In phase I, I found that the prevalence of FA in the general NL population was 5.4% and women had double the prevalence relative to men. FA was significantly associated with obesity (vs normals). Additionally, FA was positively correlated with severity of obesity. In phase II, compared to NFO, FAO individuals had lower levels of TSH, TNF-α, and amylin, but higher levels of prolactin. The total calorie intake, the dietary intake of fat and the percent calorie intake from fat and carbohydrates was higher in the FAO. FAO subjects consumed more sugar, minerals (including sodium, potassium, calcium and selenium), fat and its components, omega 3 and 6 fatty acids, vitamin D and gamma-tocopherol than NFO. The phase III by combining exome sequencing technology with genetic association analysis in 2 equally obese but with opposite extreme phenotype of FA, we discovered and validated two FA candidate genes: DRD2 and TIRAP. Our discoveries suggest that FA may represent a sub-group of obese individuals with unique nutritional, hormonal and genetic factors