The prevalence of obesity has reached epidemic proportions and is associated with the development of insulin resistance and type 2 diabetes (T2DM). A unifying theme has emerged over the past few years suggesting that lipid oversupply to metabolic organs responsible for glucose regulation leads to insulin resistance. Fitting with this, we and others have shown that increased lipid accumulation within skeletal muscle and/or liver is associated with impaired glucose uptake. However, the underlying mechanisms that mediate changes in muscle lipid metabolism are not yet known. The overall aim of this project is to examine metabolic effects of experimental weight gain in lean and overweight individuals with and without a genetic predisposition to type 2 diabetes. We hypothesise that lean subjects will increase fatty acid oxidation and upregulate mitochondrial oxidative capacity in muscle following overfeeding to protect against body weight gain and insulin resistance, but overweight subjects with a genetic predisposition to T2DM will have a defect in this ability.

Inclusion Criteria:

• Sedentary (<60 min formal exercise per week)
• Aged 20-65 years

Exclusion Criteria:

• Personal history of diabetes, cardiovascular disease or hypertension
• Recent weight change (larger than 4kg in the past 3 months)
• Smoking
• Regular use of medications, except oral contraceptives
• Individuals with alcoholism or other substance abuse
• Pregnancy or lactation, women who are planning to become pregnant or who are not using adequate measures of birth control.