1. Effect of 8 Weeks of Overfeeding on Ectopic Fat Deposition and Insulin Sensitivity: Testing the “Adipose Tissue Expandability” Hypothesis Featured Article: Darcy L. Johannsen, Yourka Tchoukalova, Charmaine S. Tam, Jeffrey D. Covington, Wenting Xie, Jean-Marc Schwarz, Sudip Bajpeyi, and Eric Ravussin Diabetes Care Volume 37: 2789-2797 October, 2014

2. STUDY OBJECTIVE Presence of large subcutaneous adipocytes in obesity may be linked to insulin resistance and type 2 diabetes through the “adipose tissue expandability” hypothesis This hypothesis has been largely formulated by cross- sectional findings and has not been prospectively demonstrated in the development of insulin resistance in humans Johannsen D. L. et al. Diabetes Care 2014;37:2789-2797

3. STUDY DESIGN AND METHODS 29 men were fed 40% more than their baseline requirement for 8 weeks Insulin sensitivity was determined using a two-step hyperinsulinemic-euglycemic clamp Intrahepatic lipid (IHL) and intramyocellular lipid (IMCL) were measured by 1H-MRS and abdominal fat by MRI Subcutaneous abdominal adipose and skeletal muscle tissues were collected to measure adipocyte size and markers of tissue inflammation Johannsen D. L. et al. Diabetes Care 2014;37:2789-2797

5. RESULTS Subjects gained 7.6 ± 2.1 kg and insulin sensitivity decreased 18% after overfeeding IHL increased 46% from 1.5 to 2.2%, but IMCL did not change There was no association between adipocyte size and ectopic lipid accumulation Subjects with smaller fat cells at baseline had a greater decrease in insulin sensitivity Johannsen D. L. et al. Diabetes Care 2014;37:2789-2797

9. CONCLUSIONS The presence of larger adipocytes did not promote ectopic lipid accumulation Smaller fat cells were associated with a worsened metabolic response to overfeeding Johannsen D. L. et al. Diabetes Care 2014;37:2789-2797