title: Prolonged Calorie Restriction Downregulates Skeletal Muscle mTORC1 Signaling Independent of Dietary Protein Intake and Associated microRNA Expression.
abstract: Short-term (5-10 days) calorie restriction (CR) downregulates muscle protein synthesis, with consumption of a high protein-based diet attenuating this decline. Benefit of increase protein intake is believed to be due to maintenance of amino acid-mediated anabolic signaling through the mechanistic target of rapamycin complex 1 (mTORC1), however, there is limited evidence to support this contention. The purpose of this investigation was to determine the effects of prolonged CR and high protein diets on skeletal muscle mTORC1 signaling and expression of associated microRNA (miR). Twelve-week old male Sprague Dawley rats consumedad libitum(AL) or calorie restricted (CR; 40%) adequate (10%, AIN-93M) or high (32%) protein milk-based diets for 16 weeks. Body composition was determined using dual energy X-ray absorptiometry and muscle protein content was calculated from muscle homogenate protein concentrations expressed relative to fat-free mass to estimate protein content. Western blot and RT-qPCR were used to determine mTORC1 signaling and mRNA and miR expression in fasted mixed gastrocnemius. Independent of dietary protein intake, muscle protein content was 38% lower (P< 0.05) in CR compared to AL. Phosphorylation and total Akt, mTOR, rpS6, and p70S6K were lower (P< 0.05) in CR vs. AL, and total rpS6 was associated with muscle protein content (r= 0.64,r2= 0.36). Skeletal muscle miR expression was not altered by either energy or protein intake. This study provides evidence that chronic CR attenuates muscle protein content by downregulating mTORC1 signaling. This response is independent of skeletal muscle miR and dietary protein.
authors.affiliation: Nutrition, Exercise, Physiology, and Sarcopenia Laboratory, U.S. Department of Agriculture Jean Mayer Human Nutrition Research Center on Aging, Tufts UniversityBoston, MA, USA; Military Nutrition Division, US Army Research Institute of Environmental MedicineNatick, MA, USA.
authors.forename: Lee M
authors.initials: LM
authors.lastname: Margolis
authors.affiliation: Nutrition, Exercise, Physiology, and Sarcopenia Laboratory, U.S. Department of Agriculture Jean Mayer Human Nutrition Research Center on Aging, Tufts University Boston, MA, USA.
authors.forename: Donato A
authors.initials: DA
authors.lastname: Rivas
authors.affiliation: Nutrition, Exercise, Physiology, and Sarcopenia Laboratory, U.S. Department of Agriculture Jean Mayer Human Nutrition Research Center on Aging, Tufts University Boston, MA, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Berrone
authors.affiliation: Nutrition, Exercise, Physiology, and Sarcopenia Laboratory, U.S. Department of Agriculture Jean Mayer Human Nutrition Research Center on Aging, Tufts University Boston, MA, USA.
authors.forename: Yassine
authors.initials: Y
authors.lastname: Ezzyat
authors.affiliation: Military Nutrition Division, US Army Research Institute of Environmental Medicine Natick, MA, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Young
authors.affiliation: Military Nutrition Division, US Army Research Institute of Environmental Medicine Natick, MA, USA.
authors.forename: James P
authors.initials: JP
authors.lastname: McClung
authors.affiliation: Nutrition, Exercise, Physiology, and Sarcopenia Laboratory, U.S. Department of Agriculture Jean Mayer Human Nutrition Research Center on Aging, Tufts University Boston, MA, USA.
authors.forename: Roger A
authors.initials: RA
authors.lastname: Fielding
authors.affiliation: Military Nutrition Division, US Army Research Institute of Environmental Medicine Natick, MA, USA.
authors.forename: Stefan M
authors.initials: SM
authors.lastname: Pasiakos
keywords: energy deficit; miR-100; miR-99; muscle protein content; rpS6