The Effect of Bariatric Surgery on Insulin Sensitivity and Energy Metabolism (BARIA-DDZ)

Dep.of General-, Visceral- and Pediatric Surgery, HHU, Duesseldorf, Dep.for Metabolic Diseases, HHU, Duesseldorf

The purpose of this study is: To explore to what extent insulin sensitivity, energy metabolism and ectopic lipid storage can be improved by bariatric surgery To explore to what extent hepatic and muscular disorders of energy metabolism occur in patients with obesity (degree 2-3) To explore whether the steato liver occurring in patients with obesity (degree 2-3) is associated with the degree of liver inflammation

Insulin resistance strongly relates to ectopic lipid deposition in skeletal muscle and the liver, which correlate with insulin resistance. Lipid metabolites accumulating in skeletal muscle and the liver are thought to impair insulin signalling and thereby reduce glucose uptake and glycogen storage. Insulin resistant humans frequently present with decreased mitochondrial function in skeletal muscle which might contribute to lipid accumulation and the development of insulin resistance. Non-alcoholic liver disease (NAFLD) comprise fatty liver, steatohepatitis and cirrhosis. NAFLD correlate with insulin resistance increased risk for cardiovascular diseases, type 2 diabetes and hepatocellular. The mechanisms leading from fatty liver to steatohepatitis and insulin resistance in the liver are yet unclear. Bariatric surgery relates to surgery for the reduction of body weight. Bariatric surgery frequently leads to normalization of glucose tolerance in previously diabetic humans even before the onset of body weight reduction. The underlying mechanisms are yet unclear. In this study we aim to explore the mechanisms underlying the onset of insulin resistance and steatohepatitis in patients with fatty liver and to identify the mechanisms leading to improved glucose tolerance in humans after bariatric surgery. We test the following hypotheses: increased lipid availability leads to (i) increased lipid oxidation and oxidative stress (ii) accumulation of lipid metabolites that impair insulin signalling (iii) bariatric surgery improves insulin sensitivity by increasing lipid oxidation. This study will contribute to the understanding of NAFLD and will help to identify new targets for the therapy of diabetes.

whole body substrate oxidation, ex vivo mitochondrial function via measurement of high resolution respirometry and in vivo mitochondrial function via measurement of ATP production

Whole body glucose uptake and endogenous glucose production as measure of skeletal muscle and hepatic insulin sensitivity

Inclusion Criteria: Aged ≥ 20 years- ≤ 70 years BMI 20- 25 kg/m 2 normal- weight group BMI 35- 39,9 kg/m 2 (Obesity grade 2) BMI >40 kg/m 2 (Obesity grade 3) Exclusion Criteria: Acute illness 2 weeks before start of examination Autoimmune or Immune disorder diseases (Leukozyten < 5000/µl Renal insufficiency (Kreatin > 1,5 mg/dl) Heart disease, condition after heart attack Anemia (Hb <12g/l, controlled before every day of examination) or blood donations 4weeks before examination. Participation in another trial within the last 2 weeks Pharmacological- immunotherapy (Cortisol, Antihistaminika, ASS) Thyroid disorders Glitazone Therapy Pregnancy, Lactation, Menstruation Smoking cigarettes, Alcohol- and drug abuse Psychiatric disorders Risk for/ or diagnosed HIV/ AIDS or Hepatitis B/C Liver disease, which are not caused by non- alcoholic steato- hepatitis Working on night shifts or irregular rhythm of night- day Impaired wound healing or clotting disorders Allergic reaction to local anesthetics Malignant cancer

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