Dardevet D, Mosoni L. Protein feeding pattern, casein feeding, or milk-soluble protein feeding did not change the evolution of body composition during a short-term weight loss program. Am J Physiol Endocrinol Metab 303: E973-E982, 2012. First published August 14, 2012; doi:10.1152/ajpendo.00285.2012.-Studies have shown that timing of protein intake, leucine content, and speed of digestion significantly affect postprandial protein utilization. Our aim was to determine if one can spare lean body mass during energy restriction by varying the quality and the timing of protein intake. Obese volunteers followed a 6-wk restricted energy diet. Four groups were compared: casein pulse, casein spread, milk-soluble protein (MSP, ϭ whey) pulse, and MSP spread (n ϭ 10 -11 per group). In casein groups, caseins were the only protein source; it was MSP in MSP groups. Proteins were distributed in four meals per day in the proportion 8:80:4:8% in the pulse groups; it was 25:25:25:25% in the spread groups. We measured weight, body composition, nitrogen balance, 3-methylhistidine excretion, perception of hunger, plasma parameters, adipose tissue metabolism, and whole body protein metabolism. Volunteers lost 7.5 Ϯ 0.4 kg of weight, 5.1 Ϯ 0.2 kg of fat, and 2.2 Ϯ 0.2 kg of lean mass, with no difference between groups. In adipose tissue, cell size and mRNA expression of various genes were reduced with no difference between groups. Hunger perception was also never different between groups. In the last week, due to a higher inhibition of protein degradation and despite a lower stimulation of protein synthesis, postprandial balance between whole body protein synthesis and degradation was better with caseins than with MSP. It seems likely that the positive effect of caseins on protein balance occurred only at the end of the experiment. lean body mass; fat mass; casein; whey; protein metabolism OBESITY HAS NOW REACHED epidemic proportions. In 2008, more than one billion adults were overweight, and 500 million were clinically obese (18). Obesity is a risk factor for the development of chronic diseases like cardiovascular diseases and diabetes, and it contributes strongly to the global burden of associated health costs. Since most medications have now been pulled from the market, obese individuals seeking weight loss often use restrictive diets. These lead to a reduction in adiposity but also to a loss of metabolically active mass, i.e., fat-free mass including muscle mass (11). This loss should be minimized. In particular, muscle is an emergency store of amino acids that are used in case of nutritional, traumatic, or infectious stresses. The objective of this work was to minimize this loss of metabolically active tissue by optimizing protein nutrition during energy restriction.It is known that lean mass wasting can be limited by including a sufficient amount of protein in the energy-restricted diet (26, 32). However, little is known about the effects of the nature and timing of ingested proteins in such situations.