Overfeeding Induced Fat-tissue Stimulation

N/ARecruitingNCT06193668

German Diabetes Center32 enrolled

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

SINGLE

Enrollment

Conditions

Lipid-induced Insulin Resistance

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 40 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Whole-body insulin sensitivity and WAT insulin sensitivity

Hyperinsulinemica-euglycemia clamp tests with deuterated glucose to measure fasting and insulin-stimulated whole-body insulin sensitivity and measurement of the index ADIPO-IR (fasting insulin x free fatty acid concentration) before and after dietary intervention period.

Time frame: 3 weeks intervention period each

Secondary Outcomes

WAT insulin signaling pathways

Adipose tissue biopsies are planned to be taken during the fasting and insulin-stimulated state before and after the dietary intervention period. DAG and ceramide subcellular fractionation assay is planned to be performed. Expressionanalyses for activation /membrane translocation of novel and atypical protein kinase C isoforms will be done. Determination of the degree of phosphorylation of various components of the insulin pathway via Western blot are planned.

Time frame: 3 weeks intervention time