Monitoring of Hepatic Fat Metabolism Using Magnetic Resonance Methods

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Monitoring of Hepatic Fat Metabolism Using Magnetic Resonance Methods

Conditions
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Hepatic Fat Content

Intervention / Treatment
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* Dietary Supplement: Fat
* Dietary Supplement: Fasting
* Dietary Supplement: Fat+Glucose
* Dietary Supplement: Glucose
* Dietary Supplement: Fat+Fructose
* Dietary Supplement: Fructose


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: 10 non-obese insulin-sensitive male volunteers with normal hepatic fat content (less than 5% of liver fat) and 10 non-obese non-diabetic subjects with increased hepatic fat content (more than 5% of hepatic fat) will undergo series of six experiments - changes of liver fat content will be measured at time 0, 3 and 6 hours after specific dietary interventions
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hepatic fat content, dietary fat, glucose, fructose, non-esterified fatty acid, triglyceride, insulin, postprandial period