Obesity is a significant and increasing health challenge. Obesity is strongly associated with the incidence of type 2 diabetes (T2D). In obese individuals, liver insulin resistance is a major factor in the development and pathophysiology of T2D. Currently, bariatric surgery is the most effective therapy for morbidly obese patients. The aim of this thesis was to study the effects of surgery-induced weight loss on glucose and lipid metabolism in the liver, and to understand the beneficial effects of bariatric surgery on fatty liver, insulin resistance and T2D. Multimodality imaging by positron emission tomography (PET) combined with magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) were utilized to study brain glucose uptake (BGU) and hepatic glucose uptake (HGU), hepatic fatty acid uptake, liver blood flow and liver fat content in morbidly obese patients (n=46) with and without T2D before and six-months after surgery (either sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB)). The results were then compared to healthy subjects. 

Preoperatively, insulin-stimulated HGU was lower in obese patients before surgery as compared to the non-obese controls. HGU increased by 30-40% after surgery as compared to the preoperative situation. Postoperatively, liver fat and endogenous glucose production (EGP) were comparable to lean controls. Before surgery, the liver fatty acid uptake was increased in obese subjects as compared to lean controls and associated with body adiposity. Liver fatty acid uptake decreased after surgery but was still high compared to controls. Portal blood flow (per volume of tissue) was increased after surgery, but as the liver volume decreased along with the surgeryinduced weight loss, the whole organ blood flow was unchanged. A positive association between BGU and EGP during insulin stimulation was found in obese subjects and the association persisted after surgery. High BGU at baseline predicted a smaller improvement in fasting plasma glucose at a 2 and 3 year follow-up. 

The results of this study suggest that bariatric surgery, either SG and RYGB, is effective in improving hepatic glucose metabolism. The persistence of high fatty acid uptake, despite a normal fat content in the liver, suggests a change in the use of fatty acids from storage to oxidation after surgery. Accelerated portal blood flow may relate to improved liver metabolism after surgery. Moreover, these findings suggest the presence of a brain-liver axis in morbidly obese individuals. This axis might contribute to further deterioration of glucose homeostasis.