Towards personalized therapy in genetic obesity

The incidence of obesity worldwide is increasing persistently, together with its associated diseases such as diabetes mellitus. Prevention is by far the most important step. It is important to pay attention to (individual) obesity causing factors, such as changes in the genetic material. These can be divided into three categories: (1) monogenic syndromic obesity, in which obesity (caused by alterations in a single gene) is accompanied by congenital malformations, dysmorphic features and/or intellectual deficit; (2) monogenic non-syndromic obesity (caused by alterations in a single gene) affecting the food satiety centre in the brain by disturbance of the leptin-melanocortin pathway; and (3) polygenic obesity, in which the effect of DNA variations in multiple genes result together in a high risk for obesity.
For patients with existing obesity, adequate treatment is requested to prevent further health damage. Besides alterations in eating habits and physical activity rate, metabolic surgery can be inevitable for some patients. The latter is currently the most effective treatment option for obesity in adults. It involves procedures to altering the anatomy of the gastrointestinal tract to induce metabolic changes and weight loss. The most frequent performed procedures are the Sleeve Gastrectomy (SG) and the Roux-en-Y Gastric Bypass (RYGB). Weight outcome varies widely and is thought to be a dynamic process. In the long term, in approximately 20-30% of the patients suboptimal weight loss or severe recurrent weight gain has been observed. One of the hypotheses is that the optimal weight response is negatively influenced by underlying obesity gene defects.