About this trial

This interventional study has 2 parts. In the part A of the project, we will determine how the acute changes in hepatic fat content (HFC) after high-fat load (150 g of fat) are affected by co-administration with three doses of glucose, fructose, and sucrose. HFC in non-obese and obese male volunteers will be measured by magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) before and at the end of 6-hour intervention. The changes in triglycerides (TG), non-esterified fatty acids (NEFA), insulin and glucose will be also measured throughout the experiments. It can be expected that most of the obese subjects will also have a non-alcoholic fatty liver disease (NAFLD) and we will be therefore able to compare the HFC response between subjects with normal liver fat content and those with steatosis.

Our previous results (doi: 10.26402/jpp.2021.1.05) clearly pointed out that glucose, contrary to fructose, prevents the storage of fat in the liver and that such an effect could be observed even after six hours. In the part B, we will therefore eliminate fructose from the diet of subjects with NAFLD of steatosis grade 2 for seven days - such an intervention will be isocaloric and fructose/sucrose will be replaced by starch or by glucose. The HFC content will be measured again by MRS and MRI after 168 hours. Very low density lipoprotein (VLDL), that transport TG out from the liver, will be isolated before and after intervention from the plasma obtained after overnight fasting. The analysis of lipid profile of the liver fat by MRS and fatty acid profile of TG in VLDL should provide an information on the role of de novo lipogenesis (DNL) in changes of HFC.

In the part A of the project we will aim

* to compare the response of HFC after high-fat load to repeated doses of glucose, fructose, and sucrose (3 x 50 g in two-hour intervals) * to compare such a response between non-obese and obese-subjects

In the part B of the project we will aim

* to find out whether short-term (7 days) restriction of fructose from the diet will decrease HFC in subjects with NAFLD * to find out whether such an intervention affects fatty acid profile of hepatic TG evaluated by MRS and by fatty acid profile of TG in VLDL - in this way we can estimate whether DNL is suppressed after fructose withdrawal * to further corroborate such an aim, we will also compare the fatty acid profile of plasma NEFA and that of TG in VLDL

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

male volunteers - 15 nonobese subjects (Body Mass Index (BMI) < 30 kg/m2) and 15 obese subjects (BMI ˃ 30 kg/m2)

18 - 70 years old

Disqualifiers

diabetes mellitus (fasting glucose above 7 mmol/l, 2-hour glucose after oGTT above 11.1 mmol/l, or antidiabetic treatment)

other serious illnesses (cardiovascular disease, cancer, etc.)

alcohol consumption ˃ 30 g/day

fructose intolerance

Trial design

Design model

Crossover

Treatments tested in this trial

150g of fat with glucose
Dietary supplement
The subjects will receive 460 ml of cream (high fat load - 150g of fat in total) with fruit tea sweetened with 50 g of glucose. Two and four hours later they will receive again fruit tea sweetened with the same sugar as at time 0 h. During the day, the subjects will not receive any food and they will be allowed to drink only water or fruit tea.
150g of fat with fructose
Dietary supplement
Description: The subjects will receive 460 ml of cream (high fat load - 150g of fat in total) with fruit tea sweetened with 50 g of fructose. Two and four hours later they will receive again fruit tea sweetened with the same sugar as at time 0 h. During the day, the subjects will not receive any food and they will be allowed to drink only water or fruit tea.
150g of fat with sucrose
Dietary supplement
The subjects will receive 460 ml of cream (high fat load - 150g of fat in total) with fruit tea sweetened with 50 g of sucrose. Two and four hours later they will receive again fruit tea sweetened with the same sugar as at time 0 h. During the day, the subjects will not receive any food and they will be allowed to drink only water or fruit tea.
Short-term (7 days) fructose restriction
Dietary supplement
Subjects will receive a package of glucose and selected foods without fructose to supplement their diet. For seven days they then will adhere to the diet without fructose and keep the detailed dietary record.

Treatment groups

40 Participants

are divided into 3 treatment groups

Group A: Part A: male subjects with BMI < 30 kg/m2Experimental treatment 3 interventions

Group B: Part A: male subjects with BMI > 30 kg/m2Experimental treatment 3 interventions

Group C: Part B: male subjects with steatosis grade 2Experimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

The comparison of the increment of hepatic fat content after high-fat load to repeated doses of glucose, fructose, and sucrose

The three examinations lasting approx. 8 hours will be carried out in each subject in the study. First, hepatic fat content will be measured using magnetic resonance imaging and magnetic resonance spectroscopy. The cannula will be then inserted into the antecubital vein and the first blood draw will be carried out. The subjects will then receive 460 ml of cream with fruit tea sweetened with 50 g of one of the sugars (glucose/fructose/sucrose). Two and four hours later they will receive again fruit tea sweetened with the same sugar as at time 0 h. The blood for biochemical analyses will be then taken at 0.5, 1, 2 (before tea), 2.5, 3, 4 (before tea), 4.5, 5 and 6 hours. The measurement of hepatic fat content will be repeated at time 6 hours. During MR examination the volume of visceral fat will be also measured and body composition will be determined. The order of examinations will be randomized and they will be carried out in at least two-week intervals.

Time frame

Three one-day measurements (8 hours) 2 weeks apart, from enrollment to the last intervention at aprox. 8 weeks

2

The comparison of the increment of HFC after high-fat load with repeated doses of simple sugar between non-obese and obese-subjects

The three examinations lasting approx. 8 hours will be carried out in each subject in the study. First, hepatic fat content will be measured using magnetic resonance imaging and magnetic resonance spectroscopy. The cannula will be then inserted into the antecubital vein and the first blood draw will be carried out. The subjects will then receive 460 ml of cream with fruit tea sweetened with 50 g of one of the sugars (glucose/fructose/sucrose). Two and four hours later they will receive again fruit tea sweetened with the same sugar as at time 0 h. The blood for biochemical analyses will be then taken at 0.5, 1, 2 (before tea), 2.5, 3, 4 (before tea), 4.5, 5 and 6 hours. The measurement of hepatic fat content will be repeated at time 6 hours. During MR examination the volume of visceral fat will be also measured and body composition will be determined. The order of examinations will be randomized and they will be carried out in at least two-week intervals.

Time frame

Three one-day measurements (8 hours) 2 weeks apart, from enrollment to the last intervention at aprox. 8 weeks

3

The comparison of hepatic fat content values after short-term (7 days) restriction of fructose from the diet in subjects with fatty liver

The fructose will be eliminated from the diet of subjects with fatty liver of steatosis grade 2 (S2) for seven days - such an intervention will be isocaloric and fructose/sucrose will be replaced by starch or by glucose. On the first day of the seven-day dietary intervention, the hepatic fat content (HFC) will be measured by magnetic resonance spectroscopy (MRS). After that they will receive a package of glucose and selected foods without fructose to supplement their diet. For seven days they then will adhere to the diet without fructose and keep the detailed dietary record. On the last day of the intervention, HFC will be measured by MRS again (after 168 hours exactly).

Time frame

From the beginning to the end of the intervention at 7 days

4

Change of hepatic fatty acid profile after short-term restriction of fructose

The hepatic fatty acid profile will be calculated from magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) data before and after short-term restriction of fructose.

Time frame

From enrollment to the analysis at 2 years

Secondary outcomes

1

Frequency of polymorphisms of PNPLA3, TM6SF2, and other genes affecting accumulation of liver fat in each study group

The frequency of gene polymorphisms (PNPLA3, TM6SF2, and others) will be compared between the group with BMI \< 30 kg/m2 and the group with BMI \> 30 kg/m2 .

Time frame

From enrollment to the analysis at aprox. 24 months

The Role of Sugars in Fat Accumulation in the Liver

About this trial

Eligibility criteria

Qualifiers

Disqualifiers

Trial design

Treatments tested in this trial

Treatment groups

Trial outcomes

Primary outcomes

Secondary outcomes

Other outcomes

Sponsors and contacts