Resolution of Liver Fat in Non-alcoholic Fatty Liver Disease

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

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.

Study Overview

• Status: Completed
• Conditions: NAFLD
• Intervention / Treatment: Other: Low carbohydrate diet

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Finland
  • Helsinki, Finland
    • RPU Diabetes and Obesity, Biomedicum
• Sweden
  • Gothenburg, Sweden
    • Wllenberg Laboratory

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Low carbohydrate diet; Isocaloric diet, <20 g carbohydrates per day	Other: Low carbohydrate diet; Isocaloric, carbohydrate restricted diet 14 days

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Helsinki University Central Hospital
• Collaborators: Göteborg University; Sahlgrenska University Hospital, Sweden
• Investigators: Principal Investigator: Marja-Riitta Taskinen, Professor, University of Helsinki

Publications and helpful links

General Publications

• Mardinoglu A, Wu H, Bjornson E, Zhang C, Hakkarainen A, Rasanen SM, Lee S, Mancina RM, Bergentall M, Pietilainen KH, Soderlund S, Matikainen N, Stahlman M, Bergh PO, Adiels M, Piening BD, Graner M, Lundbom N, Williams KJ, Romeo S, Nielsen J, Snyder M, Uhlen M, Bergstrom G, Perkins R, Marschall HU, Backhed F, Taskinen MR, Boren J. An Integrated Understanding of the Rapid Metabolic Benefits of a Carbohydrate-Restricted Diet on Hepatic Steatosis in Humans. Cell Metab. 2018 Mar 6;27(3):559-571.e5. doi: 10.1016/j.cmet.2018.01.005. Epub 2018 Feb 15.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2015
• Primary Completion (Actual): April 1, 2021
• Study Completion (Actual): December 1, 2021

Study Registration Dates

• First Submitted: September 21, 2015
• First Submitted That Met QC Criteria: September 23, 2015
• First Posted (Estimate): September 24, 2015

Study Record Updates

• Last Update Posted (Actual): April 12, 2022
• Last Update Submitted That Met QC Criteria: April 11, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver
• Other Study ID Numbers: Atkins

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO