Effect of Three Levels of Dietary Protein on Metabolic Phenotype of Healthy Individuals With 8 Weeks of Overfeeding

CONTEXT: Obesity is associated with insulin resistance and other metabolic changes that might be modified by overfeeding diets with different protein levels. OBJECTIVE: The objective of the study was to determine the effect of overfeeding diets with 5%, 15%, or 25% energy from protein on insulin sensitivity and compartments of body fat in healthy men and women. METHODS: Fifteen men and five women were overfed by approximately 40% for 56 days with 5% (low protein), 15% (normal protein), or 25% (high protein) protein diets. Insulin sensitivity was measured using a two-step insulin clamp at baseline and at 8 weeks. Body composition and fat distribution were measured by dual-energy x-ray absorptiometry and multislice computed tomography scan and abdominal sc fat cell size was determined on osmium-fixed fat cells. SETTING: This was an in-patient metabolic ward study. MAIN OUTCOME MEASURES: Insulin sensitivity and free fatty acids during low and high levels of insulin infusion before and after 8 weeks after overfeeding and changes in body fat distribution from computed tomography were measured. RESULTS: Total body fat mass, fat-free mass (FFM), visceral adipose tissue (VAT), and deep sc fat all increased with overfeeding. FFM and intrahepatic lipid increased more on the high protein diet, whereas percentage BF and fasting free fatty acids (FFAs) increased more on the low protein diet. Baseline fat cell size predicted the increase in VAT and the magnitude of FFA suppression during the high-dose insulin clamp. Acute release of insulin at baseline predicted the increase in deep sc fat but not VAT. Fasting insulin and glucose increased with overfeeding, but glucose disposal as measured by the clamp was not changed. Suppression of FFAs was less complete during the high-dose insulin infusion after overfeeding. CONCLUSION: Eight weeks of overfeeding, which increased fat mass including expansion of visceral and deep sc tissues and intrahepatic lipid, increased fasting insulin and glucose, impaired the suppression of FFA but did not produce whole-body insulin resistance