stimulating fat tissue storage with niacin to reduce fat accumulation in the liver.

Conditions: Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD); Liver Fibrosis/NASH; Non-Alcoholic Steato-Hepatitis (NASH)

Summary: metabolic dysfunction-associated steatotic liver disease (masld) (aka non-alcoholic fatty liver disease), commonly occurring in individuals with obesity and type 2 diabetes can lead to liver inflammation/ fibrosis. masld results from fat being disproportionately deposited in the liver. the goal of this mechanistic study is to investigate metabolic response in patients aged 50 to 80 years with non-alcoholic fatty liver disease, after niacin (vitamin b3) treatment. the main questions it aims to answer are: * does niacin lower the fat deposition in the liver? * does niacin raise white adipose tissue storage of dietary fatty acids? researchers will compare niacin to a placebo (a look-alike substance that contains no drug) to compare the metabolic response. duration of study per participant: up to 28 weeks

it will be a randomized crossover study with two 12-week treatment phases (niacin vs. placebo) with a 4-week washout period between the two treatment phases. the two 12-week treatment phases will be performed in random order. the treatment will be administered once daily, at the end of the largest meal. there will be a 3-week dose escalation: from 250mg (the first week) to 750mg from week 3 onward. the outcomes will be assessed at the end of each of these two treatment phases in all participants with metabolic visit a and b (i.e., a total of 4 metabolic visits). each metabolic visit will last 9 hours: it will be a test meal with perfusion of stable tracers, blood sampling, pet acquisitions using radiopharmaceuticals (18ftha and 11c-palmitate) and mri acquisitions. the two visits a and b will be performed without and with acute administration of niacin with the test meal, respectively, to determine acute niacin-induced reduction in hepatic fatty acid flux. the two visits will be performed at four to seven-day interval, in random order during the last week of each of the treatment phase.

Eligibility criteria:
inclusion criteria: * aged 50 to 80 years; * diagnosed with masld, defined as the presence of liver steatosis + abdominal obesity (as defined by the international diabetes federation country/ethnic group-specific criteria; * all women will be post-menopausal. exclusion criteria: 1. presence of advanced fibrosis (i.e., ≥ f3 based on liver stiffness \> 10kpa) using vibration-controlled transient elastography (fibroscan), serum alt \> 3 times the normal upper limit, or signs of portal hypertension \[106-109\]. 2. other hepatic disease. 3. previous diagnosis of diabetes. 4. overt cardiovascular or renal disease, cancer (other than non-melanoma skin cancer), or other uncontrolled medical conditions. 5. any contraindication to mri. 6. previous intolerance or allergy to nicotinic acid. 7. having participated to a research study with exposure to radiation in the last two years before the start of the study. 8. being allergic to eggs 9. smoking (\>1 cigarette/day) and/or consumption of \>2 alcoholic beverages per day.

Keywords: fatty liver niacin vitamin b3 nicotinic acid