The purpose of this study is to examine whether a low carbohydrate diet as compared to simple calorie restriction decreases hepatic lipid content and changes hepatic mitochondrial flux in humans.

In this study, the investigators will examine whether a low carbohydrate diet as compared to simple calorie restriction will change hepatic lipid content and mitochondrial flux in humans. Before and after a low carbohydrate diet and a simple calorie restriction intervention, rates of hepatic mitochondrial flux will be assessed using positional isotopomer analysis of 3-13C-lactate during a 3 hour basal period. Rates of whole body ketogenesis will be determined using [13C4]β-hydroxybutyrate, and whole body glucose metabolism will be measured using [2H7]glucose. Body composition will be determined with bioelectrical impedance; hepatic lipid content will be measured with MRS. Whole-body oxidation of lipids, carbohydrates and protein will be determined using indirect calorimetry.

Inclusion Criteria:

• Age 18-70
• Subjects must be able to communicate meaningfully with the investigator and must be legally competent to provide written informed consent

Exclusion Criteria:

• chronic liver disease other than NAFLD
• chronic disease associated with hepatic steatosis such as diabetes mellitus
• use of drugs known to affect hepatic steatosis
• contraindications for MRI
• pregnancy or nursing at the time of the study

IPD will be shared as much as our ethics permission and the GDPR regulations of the European Union allow