Monitoring of Hepatic Fat Metabolism Using Magnetic Resonance Methods

The first primary research objective of the study is to determine whether high-fat load (150 g of fat) induces increase in hepatic fat content (HFC) three and six hours after meal in insulin-sensitive subjects with normal HFC (<5% of fat) and in non-diabetic subjects with an increased HFC (>5% of fat). Furthermore, the other objective of the study is to determine whether the response of HFC to a high-fat load is affected by coadministration of glucose or fructose.

Study Overview

• Status: Completed
• Conditions: Hepatic Fat Content
• Intervention / Treatment: Dietary supplement: Fat; Dietary supplement: Fasting; Dietary supplement: Fat+Glucose; Dietary supplement: Glucose; Dietary supplement: Fat+Fructose; Dietary supplement: Fructose

Detailed Description

The epidemic of non-alcoholic fatty liver disease (NAFLD) is becoming a major challenge faced by health system worldwide. The hepatic fat comes from the major sources - non-esterified fatty acids (NEFA) released from adipose tissue, dietary fat and de novo lipogenesis. Fat accumulation in the liver then occurs when triglycerides (TG) that are formed are not rapidly enough oxidized or secreted from the liver in very low density lipoproteins (VLDL). It can be hypothesized that the capacity of the liver to eliminate TG can be overcome after high load of dietary fat. High-fat load should induce an immediate accumulation of hepatic fat that could be detected using 1H magnetic resonance spectroscopy (1H-MRS). The accumulation of liver fat can be also affected by coadministration of simple carbohydrates - glucose and fructose. The administration of these carbohydrates can have a pronounced impact on the availability of particular sources of hepatic fat.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Czechia
  • Prague 4, Czechia, 14021
    • Institute for Clinical and Experimental Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• normal response to oral glucose tolerance test
• normal glycated hemoglobin
• normal aspartate aminotransferase (AST)
• normal alanine aminotransferase (ALT)

Exclusion Criteria:

• BMI > 30 kg/m2
• use of pharmacological agents affecting insulin sensitivity
• use of pharmacological agents affecting lipid metabolism
• inability to undergo 1H-MRS examination

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

12

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Healthy subjects, Fat; non-obese insulin-sensitive male volunteers with normal hepatic fat content (less than 5% of liver fat) - high-fat load intervention	Dietary supplement: Fat; Subjects will consume dairy cream (150 g of fat) at time 0 hours.
Experimental: Steatosis, Fat; non-obese non-diabetic male volunteers with hepatosteatosis (more than 5% of liver fat) - high-fat load intervention	Dietary supplement: Fat; Subjects will consume dairy cream (150 g of fat) at time 0 hours.
Other: Healthy subjects, Fasting; non-obese insulin-sensitive male volunteers with normal hepatic fat content (less than 5% of liver fat) - fasting	Dietary supplement: Fasting; Subjects will fast throughout the experiment.
Other: Steatosis, Fasting; non-obese non-diabetic male volunteers with hepatosteatosis (more than 5% of liver fat) - fasting	Dietary supplement: Fasting; Subjects will fast throughout the experiment.
Experimental: Healthy subjects, Fat+Glucose; non-obese insulin-sensitive male volunteers with normal hepatic fat content (less than 5% of liver fat) - high-fat load + glucose administration	Dietary supplement: Fat+Glucose; Subjects will consume dairy cream (150 g of fat) at time 0 hours. At the same time and 2 and 4 hours later they will drink herbal tea containing 50 g of glucose.
Experimental: Steatosis, Fat+Glucose; non-obese non-diabetic male volunteers with hepatosteatosis (more than 5% of liver fat) - high-fat load + glucose administration	Dietary supplement: Fat+Glucose; Subjects will consume dairy cream (150 g of fat) at time 0 hours. At the same time and 2 and 4 hours later they will drink herbal tea containing 50 g of glucose.
Experimental: Healthy subjects, Glucose; non-obese insulin-sensitive male volunteers with normal hepatic fat content (less than 5% of liver fat) - glucose administration	Dietary supplement: Glucose; Subjects will drink herbal tea containing 50 g of glucose at times 0, 2 and 4 hours.
Experimental: Steatosis, Glucose; non-obese non-diabetic male volunteers with hepatosteatosis (more than 5% of liver fat) - glucose administration	Dietary supplement: Glucose; Subjects will drink herbal tea containing 50 g of glucose at times 0, 2 and 4 hours.
Experimental: Healthy subjects, Fat+Fructose; non-obese insulin-sensitive male volunteers with normal hepatic fat content (less than 5% of liver fat) - high-fat load + fructose administration	Dietary supplement: Fat+Fructose; Subjects will consume dairy cream (150 g of fat) at time 0 hours. At the same time and 2 and 4 hours later they will drink herbal tea containing 50 g of fructose.
Experimental: Steatosis, Fat+Fructose; non-obese non-diabetic male volunteers with hepatosteatosis (more than 5% of liver fat) - high-fat load + fructose administration	Dietary supplement: Fat+Fructose; Subjects will consume dairy cream (150 g of fat) at time 0 hours. At the same time and 2 and 4 hours later they will drink herbal tea containing 50 g of fructose.
Experimental: Healthy subjects, Fructose; non-obese insulin-sensitive male volunteers with normal hepatic fat content (less than 5% of liver fat) - fructose administration	Dietary supplement: Fructose; Subjects will drink herbal tea containing 50 g of fructose at times 0, 2 and 4 hours.
Experimental: Steatosis, Fructose; non-obese non-diabetic male volunteers with hepatosteatosis (more than 5% of liver fat) - fructose administration	Dietary supplement: Fructose; Subjects will drink herbal tea containing 50 g of fructose at times 0, 2 and 4 hours.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hepatic fat content	Change in hepatic fat content as determined by proton magnetic resonance spectroscopy (%) between 0 and 6 hours	Before time 0 hour, 3 hours, 6 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TG	Plasma triglyceride concentration	before 0, 0.5, 1, 2, 2.5, 3, 4, 4.5, 5, and 6 hours
NEFA	Plasma non-esterified fatty-acid concentration	before 0, 0.5, 1, 2, 2.5, 3, 4, 4.5, 5, and 6 hours
Glucose	Plasma glucose concentration	before 0, 0.5, 1, 2, 2.5, 3, 4, 4.5, 5, and 6 hours
Insulin	Plasma insulin concentration	before 0, 0.5, 1, 2, 2.5, 3, 4, 4.5, 5, and 6 hours
Glucagon	Plasma glucagon concentration	before 0, 0.5, 1, 2, 2.5, 3, 4, 4.5, 5, and 6 hours

Collaborators and Investigators

• Sponsor: Institute for Clinical and Experimental Medicine
• Investigators: Principal Investigator: Milan Hajek, DSc, Institute for Clinical and Experimental Medicine

Publications and helpful links

General Publications

• Dusilova T, Kovar J, Drobny M, Sedivy P, Dezortova M, Poledne R, Zemankova K, Hajek M. Different acute effects of fructose and glucose administration on hepatic fat content. Am J Clin Nutr. 2019 Jun 1;109(6):1519-1526. doi: 10.1093/ajcn/nqy386.

Study record dates

Study Major Dates

• Study Start (Actual): April 26, 2016
• Primary Completion (Actual): December 1, 2019
• Study Completion (Actual): December 1, 2019

Study Registration Dates

• First Submitted: September 4, 2018
• First Submitted That Met QC Criteria: September 19, 2018
• First Posted (Actual): September 21, 2018

Study Record Updates

• Last Update Posted (Actual): June 16, 2020
• Last Update Submitted That Met QC Criteria: June 12, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: insulin; glucose; dietary fat; fructose; triglyceride; hepatic fat content; non-esterified fatty acid; postprandial period
• Other Study ID Numbers: G285

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