The Role of Sugars in Fat Accumulation in the Liver

NCT06751862 | Recruiting

• 1 other identifier: AZV NW24J-01-00012
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Fatty Liver Disease

Keywords

hepatic fat content; magnetic resonance; fatty liver disease; diet intervention; fructosa; glucosa; sucrosa

Outcome Measures

Primary Outcomes (6)

• 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.

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

• 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.

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

• 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).

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

• 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.

  From enrollment to the analysis at 2 years

• Change of fatty acid profile of triglycerides in very low-density lipoproteins after short-term restriction of fructose

  Very low-density lipoproteins (VLDL) will be isolated by ultracentrifugation and the fatty acid profile of VLDL-triglycerides will be measured by liquid chromatography - mass spectrometry (LC-MS) in Metabolomics department of Institute of Physiology, Czech Academy of Sciences (paid service). Fatty acid profile of VLDL-triglycerides will be then compared before and after short-term restriction of fructose.

  From enrollment to the analysis at 2 years

• Change of fatty acid profile of plasma non-esterified fatty acids after short-term restriction of fructose

  Plasma free fatty acids will be carried out by liquid chromatography - mass spectrometry (LC-MS) in Metabolomics department of Institute of Physiology, Czech Academy of Sciences (paid service). Plasma free fatty acid profile will be then compared before and after short-term restriction of fructose.

  From enrollment to the analysis at aprox. 30 months

Secondary Outcomes (1)

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

  From enrollment to the analysis at aprox. 24 months

Study Arms (3)

Part A: male subjects with BMI < 30 kg/m2

EXPERIMENTAL

Only male subjects with Body Mass Index (BMI) \< 30 kg/m2 will be included in this arm. The three examinations will be carried out in each subject. The subjects will receive 460 ml of cream (high fat load - 150g of fat in total) 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.

Dietary Supplement: 150g of fat with glucose; Dietary Supplement: 150g of fat with fructose; Dietary Supplement: 150g of fat with sucrose

Part A: male subjects with BMI > 30 kg/m2

EXPERIMENTAL

Only male subjects with BMI \> 30 kg/m2 will be included in this arm. The three examinations will be carried out in each subject. The subjects will receive 460 ml of cream (high fat load - 150g of fat in total) 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.

Dietary Supplement: 150g of fat with glucose; Dietary Supplement: 150g of fat with fructose; Dietary Supplement: 150g of fat with sucrose

Part B: male subjects with steatosis grade 2

EXPERIMENTAL

Only male subjects with hepatic fat content higher than 6.2% and less than 16.5%, which corresponds to steatosis grade 2, will be included in this arm. The subjects will adhere to the diet without fructose for 7 days.

Dietary Supplement: Short-term (7 days) fructose restriction

Interventions

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.

Also known as: 460 ml of cream (high fat load - 150g of fat in total) with fruit tea sweetened with 50 g of glucose

Part A: male subjects with BMI < 30 kg/m2; Part A: male subjects with BMI > 30 kg/m2

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.

Also known as: 460 ml of cream (high fat load - 150g of fat in total) with fruit tea sweetened with 50 g of fructose

Part A: male subjects with BMI < 30 kg/m2; Part A: male subjects with BMI > 30 kg/m2

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.

Also known as: 460 ml of cream (high fat load - 150g of fat in total) with fruit tea sweetened with 50 g of sucrose

Part A: male subjects with BMI < 30 kg/m2; Part A: male subjects with BMI > 30 kg/m2

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.

Also known as: 7 days fructose restriction

Part B: male subjects with steatosis grade 2

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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
• use of drugs affecting lipid metabolism
• Part B
• male volunteers with hepatic fat content higher than 6.2% and less than 16.5%, which corresponds to steatosis grade 2 (S2)
• years old
• 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
• use of drugs affecting lipid metabolism
• intolerance of MR examination (claustrophobia, metal implants, etc.).

Sponsors & Collaborators

• Institute for Clinical and Experimental Medicine: lead
• Czech Health Research Council: collaborator

Study Sites (1)

Institute for Clinical and Experimental Medicine

Prague, Czech Republic, 14021, Czechia

RECRUITING

Related Publications (4)

• Burian M, Hajek M, Sedivy P, Mikova I, Trunecka P, Dezortova M. Lipid Profile and Hepatic Fat Content Measured by 1H MR Spectroscopy in Patients before and after Liver Transplantation. Metabolites. 2021 Sep 15;11(9):625. doi: 10.3390/metabo11090625.

  PMID: 34564441 BACKGROUND

• Hajek M, Dezortova M, Wagnerova D, Skoch A, Voska L, Hejlova I, Trunecka P. MR spectroscopy as a tool for in vivo determination of steatosis in liver transplant recipients. MAGMA. 2011 Oct;24(5):297-304. doi: 10.1007/s10334-011-0264-9. Epub 2011 Jul 10.

  PMID: 21744232 BACKGROUND

• Kovar J, Dusilova T, Sedivy P, Bruha R, Gottfriedova H, Pavlikova P, Pitha J, Smid V, Drobny M, Dezortova M, Hajek M. Acute responses of hepatic fat content to consuming fat, glucose and fructose alone and in combination in non-obese non-diabetic individuals with non-alcoholic fatty liver disease. J Physiol Pharmacol. 2021 Feb;72(1). doi: 10.26402/jpp.2021.1.05. Epub 2021 Jun 3.

  PMID: 34099584 BACKGROUND

• 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.

  PMID: 31136656 BACKGROUND

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

CD36 Antigens; Glucose; Fructose; Sucrose

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Platelet Membrane Glycoproteins; Membrane Glycoproteins; Glycoproteins; Glycoconjugates; Carbohydrates; Fatty Acid Transport Proteins; Membrane Transport Proteins; Carrier Proteins; Proteins; Amino Acids, Peptides, and Proteins; Membrane Proteins; Receptors, Cell Surface; Receptors, Immunologic; Scavenger Receptors, Class B; Receptors, Scavenger; Receptors, LDL; Receptors, Lipoprotein; Hexoses; Monosaccharides; Sugars; Ketoses; Disaccharides; Oligosaccharides; Polysaccharides

Study Officials

• Dita Pajuelo, PhD

  Institute for Clinical and Experimental Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jan Kovář, PhD

CONTACT

00420236053369; nkov@ikem.cz

Dita Pajuelo, PhD

CONTACT

00420236055348; diwa@ikem.cz

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Part A - Crossover - 2 groups of subjects receive 3 interventions in random order Part B - Single group - the same intervention for all subjects

Study Record Dates

• First Submitted: November 27, 2024
• First Posted: December 30, 2024
• Study Start: June 20, 2024
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027
• Last Updated: December 30, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

CZ (1)