The purpose of this study is:

1. To explore to what extent insulin sensitivity, energy metabolism and ectopic lipid storage can be improved by bariatric surgery
2. To explore to what extent hepatic and muscular disorders of energy metabolism occur in patients with obesity (degree 2-3)
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. Metabolic dysfunction-associated steatotic liver disease comprises steatosis, steatohepatitis and cirrhosis. MASLD correlates with insulin resistance, increased risk for cardiovascular diseases and type 2 diabetes. The mechanisms leading from steatosis to steatohepatitis and insulin resistance in the liver are yet unclear. Bariatric surgery aims at profound reduction of body weight. Also, it frequently and rapidly leads to normalization of glucose tolerance 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 steatosis 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 MASLD and will help to identify new targets for the therapy of diabetes.

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

People with obesity and various stages of MASLD, that qualify for bariatric surgery.