The Effect of Exercise Intervention on Insulin Resistance in Non-alcoholic Fatty Liver Disease (NAFLD)
The Effect of Exercise Intervention on Insulin Resistance in Non-alcoholic Fatty Liver Disease (NAFLD)
This project examines the effects of a 4 month structured exercise intervention program in
 patients with non-alcoholic fatty liver disease (NAFLD). We will examine changes in total and
 depot-specific (i.e.in different tissues, liver, muscle and pancreas)fat. We will correlate
 these with measurements of the insulin from the liver. The hypothesis is that by reducing fat
 in these specific depots we can reduce insulin resistance and prevent progression to
 diabetes.
1. Exercise program: We are asking people to take part in a supervised exercise program for
 4 months. This involves on average a weekly supervised exercise bout plus other
 unsupervised exercise bouts at home. We will ensure participants are physically able to
 embark on this by taking their medical history, physical examination and validated
 questionnaire (PARQ). This program is for the benefit on the patients' long term health.

 2. MR imaging to assess fat: occassionally these may pick up anomalies which require
 further investigation. A radiologist will screen the abdominal images and GP will be
 informed on anything requiring further investigation.

 No radiation is received during MR imaging.

 3. Physiological studies: Patients will be asked to attend for 2 non-consecutive days
 before and after the exercise intervention. Regular blood samples will be required as
 apart of these investigations.
Inclusion Criteria:

 -  Sedentary, non smoking, male subjects,

 -  Alcohol consumption men <21 units/week,

 -  BMI 27-35. (Lean individuals do not suffer from NAFLD, so are not suitable for this
 study. Conversely, we are restricted to a maximum BMI of 35 due to the size
 limitations of the MR scanner.)

 -  A clinical diagnosis of NAFLD based upon the following criteria: i) exclusion of other
 causes of liver disease i.e. negative Hepatitis B and C serology, a negative
 auto-immune profile and normal caeruloplasmin concentrations, ii) Ultrasound
 appearances suggestive of a fatty, echo-bright liver with no evidence of cirrhosis (in
 some cases, the diagnosis will have been confirmed histologically after liver biopsy.

 -  Being willing to engage and motivated to follow an exercise program.

 Exclusion Criteria:

 -  Prescription of corticosteroids, amiodarone, tamoxifen, methotrexate (drugs known to
 cause secondary steatohepatitis) or fibrates. Statin is Ok as long as the patients are
 on stable therapy for a while, if changed then the patient will be excluded.

 -  Alcohol consumption for men 21 units/week.

 -  A contraindication to exercise (such as unstable ischaemic heart disease),

 -  Type 2 diabetes (type 2 diabetes patients are excluded so that we are examining the
 involvement of insulin resistance at a reversible stage before β-cell failure has
 occurred).

 -  Patients who are on medications that will interact with GTN (glyceryl trinitrate) will
 be excluded from the GTN dilatation (endothelial independent NO mediated function)
 aspect of the study.

 -  Individuals who suffer from claustrophobia and have metal implants will be excluded
 from the MRI aspect of the study.

 -  Patients who smoke will also be excluded from the study.

 -  Total cholesterol >7