Hepatic Mitochondrial Function in Youth (MANGO)

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

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

Study Overview

• Status: Completed
• Conditions: Obesity; Bariatric Surgery Candidate; Adolescent Obesity; Hepatic Steatosis

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 20

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Anshutz Medical Campus/Children's Hospital Colorado

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years to 20 years (Child, Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Individuals age 13-20 years; Body Mass Index 35-55 m2/kg; Scheduled for Bariatric Surgery at Children's Hospital Colorado.

Description

Inclusion Criteria:

1. Obese youth ages 13-20 years, scheduled for bariatric surgery at Children's Hospital Colorado
2. BMI 35-55 m2/kg
3. Maximal body circumference <200 cm

Exclusion Criteria:

1. Use of medications known to affect insulin sensitivity: oral glucocorticoids within 10; days, atypical antipsychotics, immunosuppressant agents, HIV medications.
2. Infectious hepatitis
3. Alcohol abuse
4. Mitochondrial disease
5. Type 2 diabetes
6. Medications that affect hepatic outcomes (e.g. PPAR-γ or PPAR-α, metformin)
7. Currently pregnant or breastfeeding women. Development of pregnancy during the study period will necessitate withdrawal from the study.
8. Severe illness requiring hospitalization within 60 days
9. Diabetes, defined as Hemoglobin A1C > 6.4%
10. Anemia, defined as Hemoglobin < 10 mg/dL
11. Diagnosed major psychiatric or developmental disorder limiting informed consent
12. Implanted metal devices that are not compatible with MRI

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Percentage of Liver Fat Per MRI	Percentage of liver fat at 1 year post-bariatric surgery minus percentage of liver fat prior to bariatric surgery. Liver fat measured with MRI and calculated via the Dixon method as the proton density hepatic fat. A negative value means a decrease in liver fat after bariatric surgery.	Prior to bariatric surgery and 1 year post-bariatric surgery
Change in %Direct TG-Glycerol Appearance	Change in %TG-Glycerol appearance from a labeled glycerol drink via direct pathway. TCA substrate cycling assessed via change in fractional direct glycerol carbon contributions to newly synthesized triglycerides using a U-13C glycerol tracer drink. A higher direct percentage is beneficial, indicating decreased oxidative stress resulting from excess glycerol metabolism through the TCA cycle.	Prior to bariatric surgery and 1 year post-bariatric surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Peak Glucose	Mixed meal tolerance test (MMTT): Peak glucose concentration (mg/dL) during 4 hour MMTT with 16 time points.	Prior to bariatric surgery and 1 year post-bariatric surgery
Change in Minimum Glucose	Mixed meal tolerance test (MMTT): Minimum glucose concentration (mg/dL) during 4 hour MMTT with 16 time points.	Prior to bariatric surgery and 1 year post-bariatric surgery
Change in Peak Insulin	Mixed meal tolerance test (MMTT): Peak insulin concentration (uIU/mL) during 4 hour MMTT with 13 time points.	Prior to bariatric surgery and 1 year post-bariatric surgery
Change in Minimum Insulin	Mixed meal tolerance test (MMTT): Minimum insulin concentration (uIU/mL) during 4 hour MMTT with 13 time points.	Prior to bariatric surgery and 1 year post-bariatric surgery
Change in Peak C-peptide	Mixed meal tolerance test (MMTT): Peak c-peptide concentration (ng/mL) during 4 hour MMTT with 10 time points.	Prior to bariatric surgery and 1 year post-bariatric surgery
Change in Peak GLP-1	Mixed meal tolerance test (MMTT): Peak GLP-1 concentration (pmol/L) during 4 hour MMTT with 9 time points.	Prior to bariatric surgery and 1 year post-bariatric surgery
Mitochondrial Function in the Liver Assessed by Oroboros	L/E Coupling Control Ratio: Maximal respiratory capacity was examined in permeabilized hepatic tissue from adolescents using pyruvate (carbohydrate) and palmitoylcarnitine (lipid) as a substrate. Respiratory capacity was normalized to hepatic tissue wet weight. Coupling control ratio (L/E) was calculated as oxygen flux in leak (oligomyocin) divided by ET capacity (FCCP) with a maximum coupling of 1.0.	At the time of surgery
Change in Insulin Sensitivity	Mixed meal tolerance test (MMTT): measured with SI. This is a measure of post-prandial (MMTT) insulin sensitivity as calculated with the Oral Minimal Model (OMM) using SAAM II Software. This software uses participant weight, glucose and insulin concentrations at various time points during the MMTT to calculate the participant insulin sensitivity. A positive Si value means an increase in insulin sensitivity.	Prior to bariatric surgery and 1 year post-bariatric surgery
Change in Fasting Glucagon	Mixed meal tolerance test (MMT): Fasting glucagon concentration (pg/mL) at the beginning of a 4 hour MMTT 1 year post bariatric surgery minus prior to surgery. A negative value means there was a decrease in fasting glucagon concentrations one year post-bariatric surgery.	Prior to bariatric surgery and 1 year post-bariatric surgery
Change in Liver Stiffness Per MRI	Change from baseline in degree of hepatic stiffness, measured with Magnetic Resonance elastography (MRE).	Prior to bariatric surgery and 1 year post-bariatric surgery
Hepatic Steatosis Score Via Tissue Biopsy	NAFLD (non-alcoholic fatty liver disease) Activity Score (NAS) determined via liver tissue biopsy and graded by a pathologist. The NAS can range from 0 to 8 and is calculated by the sum of scores of steatosis (0-3), lobular inflammation (0-3) and hepatocyte ballooning (0-2). A higher number represent a worse outcome.	At the time of surgery

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Investigators: Principal Investigator: Melanie Cree-Green, MD, PhD, University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (Actual): November 20, 2018
• Primary Completion (Actual): June 21, 2023
• Study Completion (Actual): June 21, 2023

Study Registration Dates

• First Submitted: June 14, 2018
• First Submitted That Met QC Criteria: July 2, 2018
• First Posted (Actual): July 16, 2018

Study Record Updates

• Last Update Posted (Estimated): October 10, 2025
• Last Update Submitted That Met QC Criteria: September 16, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: bariatric surgery; insulin secretion; hepatic mitochondria
• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Digestive System Diseases; Liver Diseases; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Fatty Liver; Pediatric Obesity
• Other Study ID Numbers: 18-0479

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No