Cold-induced Brown Fat Activation and Hepatic Steatosis

Study Overview
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Brief Summary
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In the recent years, research on brown adipose tissue (BAT) revealed that larger amounts as well as higher activity thereof are associated with a favourable metabolic phenotype. Longitudinal studies which applied recurrent cooling sessions demonstrated a high plasticity of BAT which significantly increased in size and activity during these studies. These changes were accompanied by improvements in body fat mass as well as insulin sensitivity. Non-alcoholic fatty liver disease (NAFLD) is estimated to advance to the primary cause of liver cirrhosis and hepatocellular carcinoma in the following years. Besides predisposing genetic and possibly nutritional factors, the insulin resistance syndrome and obesity are the main factors contributing to this excessive hepatic lipid accumulation. The aim of this study is to investigate whether BAT recruitment via cold-acclimation results in decreased hepatic lipid content in overweight/obese patients with NAFLD.

Official Title
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Cold-induced Brown Fat Activation and Hepatic Steatosis

Conditions
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Non-Alcoholic Fatty Liver Disease

Intervention / Treatment
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* Other: Cold exposure


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: body mass index 28 - 40 kg/m^2 hepatic lipid content > 10 % Exclusion Criteria: endocrine disease, except treated hypo-/hyperthyroidism and hypertriglyceridemia (<500 mg/dl) and untreated type II diabetes mellitus (fasting glucose < 140 mg/dl) use of beta-blockers, alpha-blockers and rilmenidine chronic kidney disease inflammatory bowel disease active malignant disease autoimmune disease chronic alcohol abuse or alcohol consumption greater than 30g/d for men or 20 g/d for women transferrin saturation > 40% serum alpha-1 antitrypsin < 90 mg/dl serum ceruloplasmin < 20 mg/dl positive serology for autoimmune hepatitis positive hepatitis serology liver cirrhosis portal hypertension pregnancy contraindications for magnetic resonance imaging

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cold exposure<br> | Other: Cold exposure<br>* Two hours of mild cold exposure using a water-perfused vest<br>|
| No Intervention: Room temperature<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hepatic lipid content (%) | Magnetic resonance imaging-proton density fat fraction | Six weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brown adipose tissue volume (ml) / activity (SUVmean) | 18-fluorodeoxyglucose positron emission tomography/ magnetic resonance imaging | Six weeks | 
| Basal metabolic rate (kcal/day/kg fat-free body mass) | Indirect calorimetry | Six weeks | 
| Cold-induced non-shivering thermogenesis (%) | Indirect calorimetry: percentage increase in basal metabolic rate before and after cold exposure | Six weeks | 
| Body fat mass (kg) | Air displacement plethysmography | Six weeks | 
| Insulin sensitivity | Matsuda Index for 2 hour standard oral glucose tolerance test | Six weeks |