Overview
Type 2 diabetes is the most common metabolic disease worldwide, characterized by hyperglycemia, decreased whole body insulin sensitivity, and white adipose tissue (WAT) dysfunction. A key factor in its development is chronic overnutrition, usually with a high-fat diet (HFD), leading to disturbances of glucose and lipid metabolism. However, the mechanism of short-term HFD-induced tissue-specific insulin resistance remains poorly understood. This project aims to further unravel the underlying mechanisms of short-term HFD overnutrition-mediated WAT insulin resistance. The model described here corresponds to a randomized, single- blinded parallel-grouped trial, consisting of two interventions: a macronutrient-balanced diet and or a hypercaloric diet over three weeks in order to investigate differences in interorgan fatty acid and glucose metabolism between the studied groups. Based on recent studies, the hypothesis is that 21-day hypercaloric HFD induces WAT insulin resistance via a diacylglycerol, novel protein kinase C-insulin receptor signaling model in both fasting and insulin-stimulated states.
Eligibility
Inclusion Criteria:
- Age between 18 and 40 years
- BMI < 29 kg/m2
- Sport inactive (<1x /week)
- Capacity to consent
Exclusion Criteria:
- Diabetes mellitus disease
- Acute coronary heart syndrome (myocardial infarction, unstable angina pectoris, stroke or transient ischemic attack in the last 3 months before study participation)
- Acute infectious disease
- Taking blood glucose-lowering drugs
- Diseases or drugs affecting the immune system and allergies to drugs used in the study
- Drugs with potential metabolic effects
- Chronic liver disease (hepatitis, gallbladder disease, elevated liver enzymes (ALT > 300 U/L))
- Chronic inflammatory bowel diseases
- Rheumatic diseases
- Hyper- or hypothyroidism of the thyroid gland
- Renal insufficiency, administration of iodine-containing contrast media in the last 2 days
- Chronic lung diseases
- cancerous diseases
- Addictive diseases, psychiatric diseases
- Pregnancy, breastfeeding
- Shift workers
- Anemia (Hb <12 g/dl)
- Disorders of hemostasis
- Regular use of antithrombotic drugs
- Alcohol consumption, smoking
- Conditions that do not permit an MRI examination