Hepatic Mitochondrial Function in Youth

Study Overview
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Brief Summary
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Assess the impact of bariatric surgery on hepatic energy metabolism and glucose and insulin dynamics in obese youth

Detailed Description
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A metabolic study that will be performed prior to and 12 months following bariatric surgery. The study will include 31-phosphorus magnetic resonance spectroscopy to measure phosphate concentrations in the liver; a 4 hour mixed meal tolerance test, an intravenous arginine test, Abdominal Magnetic Resonance Imaging (MRI) for visceral and hepatic fat, Magnetic Resonance (MR) Elastography of the liver, indirect calorimetry, body composition assessment with Bodpod, serum metabolomics and hepatic tissue mitochondrial measures from the time of surgery only.

Official Title
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Hepatic Fat Content and Mitochondrial Flux in Obese Youth Before and After Bariatric Surgery

Conditions
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Hepatic Steatosis, Bariatric Surgery Candidate, Adolescent Obesity, Obesity

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Obese youth ages 13-20 years, scheduled for bariatric surgery at Children's Hospital Colorado BMI 35-55 m2/kg Maximal body circumference <200 cm Exclusion Criteria: Use of medications known to affect insulin sensitivity: oral glucocorticoids within 10; days, atypical antipsychotics, immunosuppressant agents, HIV medications. Infectious hepatitis Alcohol abuse Mitochondrial disease Type 2 diabetes Medications that affect hepatic outcomes (e.g. PPAR-γ or PPAR-α, metformin) Currently pregnant or breastfeeding women. Development of pregnancy during the study period will necessitate withdrawal from the study. Severe illness requiring hospitalization within 60 days Diabetes, defined as Hemoglobin A1C > 6.4% Anemia, defined as Hemoglobin < 10 mg/dL Diagnosed major psychiatric or developmental disorder limiting informed consent Implanted metal devices that are not compatible with MRI

Ages Eligible for Study
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Minimum Age: 13 Years
Maximum Age: 20 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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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Hepatic mitochondrial function | Hepatic mitochondrial function will be measured with 31 phosphorus MR Spectroscopy: Hepatic mitochondrial function | Prior to bariatric surgery and 1 year post-bariatric surgery | 
| Changes in Hepatic mitochondrial function | Hepatic mitochondrial function will be measured with 31 phosphorus MR Spectroscopy Magnetic Resonance Imaging: MRE, hepatic fat fraction. | Prior to bariatric surgery and 1 year post-bariatric surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Insulin Resistance/pancreas/GI hormones | Mixed meal tolerance test (MMT): Insulin sensitivity to determine maximal insulin secretion. | Prior to bariatric surgery and 1 year post-bariatric surgery | 
| Changes in Insulin Resistance/pancreas/GI hormones | Mixed meal tolerance test (MMT): Hyperglycemia to determine maximal insulin secretion | Prior to bariatric surgery and 1 year post-bariatric surgery | 
| Changes in Insulin Resistance/pancreas/GI hormones | Mixed meal tolerance test (MMT): Hypoglycemia to determine maximal insulin secretion | Prior to bariatric surgery and 1 year post-bariatric surgery | 
| Changes in Insulin Resistance/pancreas/GI hormones | Mixed meal tolerance test (MMT): Insulin/C-peptide response to determine maximal insulin secretion | Prior to bariatric surgery and 1 year post-bariatric surgery | 
| Changes in Insulin Resistance/pancreas/GI hormones | Mixed meal tolerance test (MMT): GLP-1 to determine maximal insulin secretion | Prior to bariatric surgery and 1 year post-bariatric surgery | 
| Insulin Resistance/pancreas/GI hormones | Mixed meal tolerance test (MMT): Glucagon response to determine maximal insulin secretion | Prior to bariatric surgery and 1 year post-bariatric surgery | 
| NAFLD via MRI | Changes, if any, will be documented through the use of Magnetic Resonance (MR) elastography. | Prior to bariatric surgery and 1 year post-bariatric surgery | 
| Changes in Tissue hepatic glycerol flux | Glucose will be assessed with Oroboros, isotopomer flux will be determined by 13c glycerol tracer | At time of surgery | 
| Changes in Tissue hepatic mitochondrial function | Fat oxidation will be assessed with Oroboros | At time of surgery | 
| Changes in NAFLD status via tissue | NAFLD status will be determined by biopsy at the time of surgery | At time of surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bariatric surgery, hepatic mitochondria, insulin secretion