Resolution of Liver Fat in Non-alcoholic Fatty Liver Disease

Study Overview
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Brief Summary
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The major adverse health consequences of obesity occur only when non-alcoholic fatty liver disease (NAFLD) also develops. NAFLD is characterized by abnormal hepatic accumulation of triglycerides and other lipids. The first-line approach to NAFLD management is caloric restriction and weight loss, but these remain difficult to achieve. Little attention has been given to dietary carbohydrate restriction, despite recent reports showing that hepatic de novo lipogenesis, a process that converts dietary carbohydrates into fatty acids in the postprandial state, accounts for approximately 25% of liver triglyceride content in hyperinsulinemic subjects with NAFLD. For comparison, only 15% of the liver triglycerides were derived from dietary fatty acids in patients with NAFLD who had consumed a standardized 30% fat diet for four days before being assessed.

Detailed Description
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To establish the time-course of hepatic fat loss in NAFLD subjects on a carbohydrate-restricted diet (<20 g/day), a serial assessments of liver fat during two week diet will be performed. Also, markers of lipid and insulin metabolism, liver function test and changes in gut microbiota during rapid metabolic improvement will be assessed. The overall aim is to exploit this unique set of human material to determine the specific cellular and molecular pathways that are modified in the early stages of metabolic improvement and fatty liver regression.

Official Title
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Rapid Resolution of Human Fatty Liver Disease, the Key to Obesity-related Morbidity and Mortality

Conditions
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NAFLD

Intervention / Treatment
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* Other: Low carbohydrate diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: increased liver fat above 5 % in magnetic resonance spectroscopy body mass index 27-39.9 kg/m2 Exclusion Criteria: liver cirrhosis portal hypertension chronic liver disease other than NAFLD diabetes mellitus or other significant endocrine disease any medication acting on nuclear hormone receptors or inducing liver enzymes or self-administration of supplements other than calcium or vitamins/trace elements any significant cardiovascular co-morbidity history of non-compliance genotype (PNPLA3-MM and TM6SF2-TT) promoting liver fat accumulation

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

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: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Low carbohydrate diet<br>Isocaloric diet, <20 g carbohydrates per day | Other: Low carbohydrate diet<br>* Isocaloric, carbohydrate restricted diet 14 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Liver fat percent by nuclear magnetic resonance imaging | Liver fat percent measured by nuclear magnetic resonance imaging | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| De novo lipogenesis measured as Incorporation of new fatty acids (%) to very-low density lipoprotein triglycerides |  | 14 days | 
| Gut microbiota measured as change in microbiome profile from baseline |  | 14 days |