Diet, Immunometabolism and Non-alcoholic Fatty Liver Disease

Immunometabolic Effects of Time Restricted Eating in Non-alcoholic Fatty Liver Disease

This study will assess the impact of 8-hour time restricted eating (8 hours of eating, 16 hours fasting) combined with a Mediterranean diet on metabolism and inflammation in adults with non-alcoholic fatty liver disease (NAFLD).

Non-alcoholic fatty liver disease (NAFLD), defined as the accumulation of fat in the liver that is not related to alcohol intake, is the number 1 global cause of chronic liver disease. Excessive consumption of energy, saturated fat, and simple sugars is a key contributor to hepatic lipid accumulation and obesity-induced metabolic inflammation, reflecting cross-talk between immune and metabolic pathways. Moreover, dietary factors including saturated fatty acids, cholesterol, and their derivatives, as well as gut-derived metabolites, can prime innate immune cells to induce an exaggerated pro-inflammatory response upon re-exposure to such stimuli and may contribute to chronic low grade inflammation.

Dietary strategies focusing on replacing inflammatory dietary triggers with monounsaturated fats, fiber and complex carbohydrates have been shown to improve metabolic dysfunction, but how this relates to a rewiring of the innate immune system is less clear. Time-restricted eating (TRE) is another dietary strategy which has been shown to elicit beneficial effects that reduce the risk of chronic metabolic disease and consolidates eating to a 6-10 hour period daily. Early TRE (eTRE), wherein eating occurs from morning to early afternoon, is associated with greater cardiometabolic health benefits than eating late in the evening. This includes improved insulin sensitivity, glucose tolerance and lipid metabolism, and reduced inflammatory markers.

This study will determine the impact of an 8-week intervention of 8-hour eTRE combined with an anti-inflammatory Mediterranean diet on the metabolic and immune phenotype of individuals with NAFLD, a population at high risk of progressive cardiometabolic decline and chronic inflammation. By focusing on improving both nutrient quality and nutrient timing, a greater understanding of the interaction between systemic metabolism and immune cell rewiring will be gained.

Inclusion Criteria:

• Males and females
• Age 18-65 years, from all ethnic groups, capable of providing informed consent to participate
• Obesity (body mass index >30kg/m^2) and of stable body weight (±3% for ≥3 months)
• Fasting blood glucose <7.0 mmol/L and HbA1c <6.5%.
• Liver fat >10% (CAP score >238 dB/m) and no fibrosis (liver stiffness score 2-7 kPa) as assessed by liver elastography (FibroScan)

Exclusion Criteria:

• Impaired renal function
• Abnormal hematocrit
• History of cardiovascular events
• Uncontrolled hypertension
• Type 2 diabetes
• Medications or supplements known to affect glucose or lipid metabolism
• Active inflammatory, autoimmune, infectious, gastrointestinal, or malignant disease
• Uncontrolled neurological or psychiatric disease
• Iron deficiency anemia, (hemoglobin < 12g/dl men, < 11g/dl women)
• Fatty acid supplements and consumers of high doses of anti- antioxidant vitamins (A, C, E, b-carotene)