Prospective, Randomised Study: Metabolic and Functional Effects of Bariatric Surgery Accessed Using Positron Emission Tomography (PET) and MRI. (Sleevepet2)

Diet and nutrition are important factors in the maintenance of good health throughout the entire life course. Their role as determinants of chronic diseases such as obesity, diabetes and cardiovascular diseases is well established. The annual increase in the prevalence and the severity of obesity in both adults and children is currently substantial, and in Finland 40% of adults are overweight or obese. Identifying the mechanisms that make some individuals vulnerable to overeating, as well as pinpointing how obesity changes the functioning of the human mental and bodily functions would be critical for understanding the current high prevalence of obesity.

Animal studies suggest that the brain extensively coordinates the adaptive mechanisms and the alterations of energy intake and expenditure. Accumulating evidence suggest that obesity is associated with changes in brain morphology and function, thus the source for obesity may lie in the brain. In the present project the investigators test this hypothesis by implementing a multimodal neuroimaging approach with positron emission tomography (PET), functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI) and voxel-based morphometry (VBM). By studying brain anatomy and function in lean individuals as well as obese patients undergoing weight loss surgery, the investigators can evaluate whether the observed differences between lean and obese individuals are causes or consequences of obesity. In PET imaging of the brain, the investigators will focus on two specific neurotransmitter systems, dopamine and opioid, which are largely been unexplored in obesity research.

Obesity is related to elevated plasma glucose levels and endothelial dysfunction. Elevated plasma glucose and endothelial dysfunction are known risk factors for diabetes and coronary heart disease.

Weight reduction modifies risk factors such as blood pressure and lipid profile for chronic diseases. On this study the investigators are able to further investigate changes in fatty acid metabolism and hormones affecting feeding and energy balance. In addition, changes in brain activation in response to food stimuli will be assessed. As far as the investigators know there are no previous positron emission tomography (PET) studies that investigate these risk factor variables from one study population pre-operatively and after bariatric surgery.

The objectives of this study are to measure effect of obesity on brain structure and molecular pathways, food-stimuli mediated brain activation response, on hormones affecting both feeding and energy balance as well as on bone metabolism and bone marrow fat. The study consists of two phases. In the first phase the studies are performed at baseline before bariatric surgery and in the second phase post-operatively after 6 months. Regional free fatty acid uptake in myocardium, skeletal muscle, subcutaneous fat, visceral fat, pancreas, liver, brain, intestine and the bone are studied with PET and 14(R, S)-[18F]-fluoro-6-thia-heptadecanoic acid ([18F]FTHA). Changes in body fat distribution, in ectopic fat and fat content of key organs are investigated with magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). ). Cardiac functioning is studied with echocardiography and functional MRI (fMRI) and ectopic fat in and around the heart using MRI and MRS. Brain reward system response to food stimuli is assessed using functional MRI (fMRI) and white and grey matter volumes using diffusion tensor imaging (DTI). Brain neurotransmitter system will be measured with [11C]raclopride and [11C]carfentanil and PET. In the second part of the study the same variables are studied after bariatric surgery: either laparoscopic sleeve gastrectomy or Roux-en-Y gastric bypass. The objective is also to study whether less invasive sleeve gastrectomy is as beneficial in terms of weight loss and co-morbid diseases as more invasive Roux-en-Y gastric bypass and to compare the changes in tissue metabolism between these two surgical procedures.

The study consists totally of 60 study subjects. Of these 40 are morbidly obese adults, BMI