Defining Circadian Metabolism in Non-alcoholic Fatty Liver Disease

Defining Circadian Metabolism in Non-alcoholic Fatty Liver Disease

The investigators will conduct an open label, experimental medicine study exploring the diurnal patterns of hepatic lipid metabolism in NAFLD and non-NAFLD participants (determined by Transient elastography (TE) with controlled attenuation parameter (CAP)). We will also determine whether the diurnal patterns of lipid metabolism in NAFLD participants can be modified using lifestyle and weight loss intervention. Fourteen participants without NAFLD will have morning and evening metabolic investigations (visit 1M & 1E) to assess for changes in lipid flux pathways across the course of the day. After morning and evening investigations their involvement in the clinical study will then end. Seventeen NAFLD participants will also have identical baseline morning and evening investigation after which they will be enrolled into a 12-week lifestyle and weight loss programme. After 12-weeks, all 17 participants with NAFLD will have a follow up CAP, and morning and evening metabolic investigations (visit 2M & 2E).

Inclusion Criteria:

• Male or female
• BMI 25-50 kg/m2
• Age 18-75 years

Exclusion Criteria:

• A diagnosis of type 1 diabetes
• Type 2 diabetes controlled with medications other than metformin (within last 3 months)
• Shift working patterns in last 3-months or if likely to work shifts during study period.
• Current or recent (<3-months) use of weight loss medications
• Current or recent use of oral contraceptive pill or hormone replacement therapy (within last 3-months)
• Pregnancy
• A blood haemoglobin <120mg/dL
• History of alcoholism or a greater than recommended alcohol intake (Recommendations > 21 units on average per week for men and > 14 units on average per week for women)
• Haemorrhagic disorders
• Treatment with anticoagulant agents
• Other co-morbidities that in the eyes of the investigators may affect data collection
• Any medical condition in the opinion of the investigator that might impact upon safety or validity of the results
• Transient elastography (TE) controlled attenuation parameter (CAP) of between 216-305 dB/m