Dopamine action on metabolism depending on genetic heterogeneity – a randomized, placebo-controlled double blind study (Dopamine Genetics)

So far, the origin of obesity, regardless of an existing positive energy balance, is not fully understood. In addition to environmental factors, the genetic background plays an important role in the pathogenesis of obesity. Common genetic polymorphisms, variants in the fat mass and obesity associated gene (FTO) locus have the highest effect size on body weight. Animal and first clinical studies indicate that FTO variants interact with dopamine signaling in the brain, thus contributing to the risk for overweight. In fact, preliminary results indicate that enhancing dopamine signaling with the dopamine agonist bromocriptine, depending on the FTO genotype, either induces weight loss or has a neutral effect on body weight.

The study is a randomized, double-blind, placebo-controlled multicenter clinical trial conducted in four sites of the German Center for Diabetes Research (DZD), with the lead center being Tübingen. In this trial, 150 participants with obesity (BMI ≥ 30 kg/m²) are randomized to receive 5 mg bromocriptine qd or placebo. The subjects are stratified according to their FTO genotype. Before and after treatment, brain insulin sensitivity is assessed by functional MRI combined with intranasal administration of insulin to the brain. All participants undergo a 75 g oral glucose tolerance test to evaluate glucose tolerance, peripheral insulin sensitivity and insulin secretion before and after treatment. Body fat is assessed by whole-body MRI and intrahepatic fat by localized MR-spectroscopy. Resting energy expenditure and respiratory quotient are measured by indirect calorimetry. 

  

With the study we pursue two main objectives

  • To develop a genotype-specific and thus individualized therapy approach for obesity.
  • We aim to assess the effect of bromocriptine on brain insulin sensitivity, cognitive function, body fat as well as body fat distribution and glycaemia.

Project supervisor

Prof. Dr. Martin Heni

Study registration

NCT03525002

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