Hepatic and Cardiac Metabolic Flexibility in Obese With NAFLD.

The Effect of Physical Activity on the Liver and the Heart's Metabolism of Fatty Acids in Obese With and Without NAFLD

Non-alcoholic fatty liver disease (NAFLD) covers a spectrum from reversible hepatic steatosis to inflammation and fibrosis termed steatohepatitis (NASH) and cirrhosis. New evidence indicates that NAFLD is associated with development of heart failure, abnormal ventricular glucose and fatty acid (FA) utilisation and cardiosteatosis. The mechanisms behind cardiac involvement and the progression from NAFLD to NASH are poorly understood but must include altered cardiac and intrahepatic lipid handling. In collaboration with renowned research groups from Oxford, Mayo Clinic and Copenhagen investigators plan comprehensive kinetic studies of heart and liver FA uptake and oxidation, ventricular function and substrate utilisation, and hepatic triglyceride (TG) secretion in order to assess mechanisms governing cardiac and hepatic lipid and glucose trafficking in subjects with NAFLD and NASH and the relationship with heart function. In addition, the investigators will assess skeletal muscle and adipose tissue enzyme activities, gene expression and protein concentrations in these subjects to define mechanisms involved in the cross-talk between heart, liver, muscle and adipose tissues. Investigators will address these questions using innovative tracer techniques (11Cpalmitate, 11C acetate, 18FDG glucose PET tracers and TG tracers) in combination with hepatic vein catherisation to study cardiac and liver substrate trafficking, as well as NMR spectroscopy, echocardiography, muscle and fat biopsies in combination with state-of-the art muscle and adipose tissue enzyme kinetics, gene- and protein expression. Effects of acute exercise will be assessed. The overarching goals are to define abnormalities and differences between NAFLD and NASH in hepatic lipid (FA and TG) metabolism and to assess the effect of exercise on both hepatic, cardiac and adipose and skeletal muscle lipid and substrate utilisation.

Study Overview

• Status: Completed
• Conditions: NAFLD - Nonalcoholic Fatty Liver Disease
• Intervention / Treatment: Behavioral: Exercise

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Aarhus N
    • Skejby, Aarhus N, Denmark, 8200
      • Department of Diabetes and Hormone diseases in Aarhus University Hopital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 10 obese subject men/women with NAFLD (MR spectroskopi, fibro scanner) (BMI > 30).
• 10 obese subject men/women without NAFLD (MR spectroskopi, fibro scanner) (BMI > 30).
• age between 40-70 years
• Written consent before the start of the study

Exclusion Criteria:

• known current disease
• Fixed Medical drug consumption, statins and antihypertensive drugs (non-beta blocker). However, pause 3 weeks before the examination date
• Blood donation within the last 3 months prior to the study
• Participation in experiments involving radioactive isotopes within the last 6 months
• Alcohol abuse (over 21 items per week for men and 14 for women)
• Smoking
• Weight over 130 kg
• Cancer patients
• Large intake of medication

Study Plan

How is the study designed?

Design Details

• Primary Purpose: HEALTH_SERVICES_RESEARCH
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Healthy male volunteers; Behavioral: Exercise Moderate Intensity Exercise (50 % af VO2max) for 90 minutes before and after PET scanning.	Behavioral: Exercise; Moderate Intensity Exercise (50 % af VO2max) for 90 minutes
EXPERIMENTAL: Healthy female volunteers; Behavioral: Exercise Moderate Intensity Exercise (50 % af VO2max) for 90 minutes before and after PET scanning.	Behavioral: Exercise; Moderate Intensity Exercise (50 % af VO2max) for 90 minutes

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The effect of physical activity on the heart's metabolism of fatty acids in obese with and without NAFLD	Primary outcome: - Fatty acid uptake (mg/kg/min) in the Heart in obese with and without NAFLD	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine the effect of an acute exercise bout on the improvement of cardiac FA utilization in obese with and without NAFLD.	Fatty acid oxidation (µmol/min) in the Heart in obese with and without NAFLD.	2 years

Collaborators and Investigators

• Sponsor: University of Aarhus

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 3, 2018
• Primary Completion (ACTUAL): September 7, 2020
• Study Completion (ACTUAL): May 23, 2022

Study Registration Dates

• First Submitted: May 22, 2018
• First Submitted That Met QC Criteria: June 28, 2018
• First Posted (ACTUAL): July 11, 2018

Study Record Updates

• Last Update Posted (ACTUAL): May 24, 2022
• Last Update Submitted That Met QC Criteria: May 23, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: jeyanrk

Drug and device information, study documents

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