The Role of Sugars in Fat Accumulation in the Liver

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

Eligibility

Part A

Inclusion Criteria:

* male volunteers - 15 nonobese subjects (Body Mass Index (BMI) \< 30 kg/m2) and 15 obese subjects (BMI ˃ 30 kg/m2)
* 18 - 70 years old

Exclusion Criteria:

* 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

Inclusion Criteria:

* male volunteers with hepatic fat content higher than 6.2% and less than 16.5%, which corresponds to steatosis grade 2 (S2)
* 18 - 70 years old

Exclusion Criteria:

* 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.).

Conditions2

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