About this trial
This prospective, single-center pilot study will evaluate metabolic flux dysregulation in adults with obesity and suspected or confirmed metabolic dysfunction-associated steatotic liver disease (MASLD) who are scheduled for protocol-eligible bariatric surgery at Vanderbilt University Medical Center. Participants will undergo research assessments before surgery, during the planned bariatric surgery encounter, and approximately 6 months after surgery. The study uses non-radioactive stable isotope tracer infusions, serial blood sampling, abdominal MRI/MRE, and research tissue specimens collected only during clinically planned bariatric surgery to quantify hepatic and extrahepatic metabolic fluxes. The primary objective is to determine how hepatic citric acid cycle flux and related metabolic pathways change after bariatric surgery and how these metabolic measures relate to liver fat, liver stiffness, and biopsy-graded MASLD/MASH severity.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Scheduled and clinically cleared for protocol-eligible bariatric surgery at Vanderbilt University Medical Center.
BMI ≥40 kg/m², or BMI >35 kg/m² with at least one obesity-associated comorbidity, such as type 2 diabetes, cardiovascular disease, hypertension, hyperlipidemia, obstructive sleep apnea, MASLD, osteoarthritis, or polycystic ovarian syndrome.
Able and willing to complete study procedures, including informed consent, questionnaires, blood draws, MRI/MRE imaging, stable isotope tracer infusion, and research tissue collection during planned bariatric surgery.
Able to provide informed consent in English.
Disqualifiers
Contraindication to MRI/MRE, including implanted cardiac defibrillator, pacemaker, or other MRI-incompatible implanted device.
Prior gastric or intestinal surgery, pancreatic surgery, or other prior surgery that, in the judgment of the study team or bariatric surgeon, would interfere with study procedures or outcome interpretation.
Active cancer or ongoing cancer treatment.
Presence or history of HIV infection.
Trial design
Single group
Treatments tested in this trial
Bariatric surgery
Procedure/SurgeryClinically indicated bariatric surgery, such as Roux-en-Y gastric bypass or sleeve gastrectomy, performed as part of standard clinical care.
Stable isotope tracer infusion
Other interventionIntravenous non-radioactive stable isotope tracers administered for research measurement of metabolic flux: \[¹³C₃\]lactate, \[6,6-²H₂\]-D-glucose, and \[9,9-²H₂\]palmitate.
MRI/MRE
Diagnostic testAbdominal MRI proton density fat fraction and magnetic resonance elastography to assess hepatic fat and stiffness before surgery and approximately 6 months after surgery.
Research tissue collection during planned bariatric surgery
Procedure/SurgeryLiver, omentum, subcutaneous adipose tissue, and skeletal muscle specimens collected only during clinically planned bariatric surgery and only if safe in the surgeon's judgment.
Treatment groups
Trial outcomes
Primary outcomes
Change in hepatic citric acid cycle flux after bariatric surgery
Change in hepatic citric acid cycle flux estimated from stable isotope enrichment patterns, including \[¹³C₃\]lactate-based measurements, before bariatric surgery and approximately 6 months after surgery.
Secondary outcomes
Change in hepatic gluconeogenic flux
Estimated from plasma glucose isotope enrichment and metabolic flux modeling
Change in endogenous glucose production
Estimated using \[6,6-²H₂\]-D-glucose tracer dilution
Change in free fatty acid turnover
Estimated using \[9,9-²H₂\]palmitate tracer dilution
Change in lactate turnover / lactate-related flux
Estimated using stable isotope enrichment patterns
Locations
Sponsors and contacts
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