title: Calorie Restricted High Protein Diets Downregulate Lipogenesis and Lower Intrahepatic Triglyceride Concentrations in Male Rats.
abstract: The purpose of this investigation was to assess the influence of calorie restriction (CR) alone, higher-protein/lower-carbohydrate intake alone, and combined CR higher-protein/lower-carbohydrate intake on glucose homeostasis, hepatic de novo lipogenesis (DNL), and intrahepatic triglycerides. Twelve-week old male Sprague Dawley rats consumed ad libitum (AL) or CR (40% restriction), adequate (10%), or high (32%) protein (PRO) milk-based diets for 16 weeks. Metabolic profiles were assessed in serum, and intrahepatic triglyceride concentrations and molecular markers of de novo lipogenesis were determined in liver. Independent of calorie intake, 32% PRO tended to result in lower homeostatic model assessment of insulin resistance (HOMA-IR) values compared to 10% PRO, while insulin and homeostatic model assessment of β-cell function (HOMA-β) values were lower in CR than AL, regardless of protein intake. Intrahepatic triglyceride concentrations were 27.4 ± 4.5 and 11.7 ± 4.5 µmol·g(-1) lower (p < 0.05) in CR and 32% PRO compared to AL and 10% PRO, respectively. Gene expression of fatty acid synthase (FASN), stearoyl-CoA destaurase-1 (SCD1) and pyruvate dehydrogenase kinase, isozyme 4 (PDK4) were 45% ± 1%, 23% ± 1%, and 57% ± 1% lower (p < 0.05), respectively, in CR than AL, regardless of protein intake. Total protein of FASN and SCD were 50% ± 1% and 26% ± 1% lower (p < 0.05) in 32% PRO compared to 10% PRO, independent of calorie intake. Results from this investigation provide evidence that the metabolic health benefits associated with CR-specifically reduction in intrahepatic triglyceride content-may be enhanced by consuming a higher-protein/lower-carbohydrate diet.
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 02111, USA. Lee.Margolis@Tufts.edu.|Military Nutrition Division, U.S. Army Research Institute of Environmental Medicine, Natick, MA 01760, USA. Lee.Margolis@Tufts.edu.
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 02111, USA. Donato.Rivas@Tufts.edu.
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 02111, USA. Yassine.Ezzyat@Tufts.edu.
authors.forename: Yassine
authors.initials: Y
authors.lastname: Ezzyat
authors.affiliation: Military Performance Division, U.S. Army Research Institute of Environmental Medicine, Natick, MA 01760, USA. Erin.G.Stomberg.civ@mail.mil.
authors.forename: Erin
authors.initials: E
authors.lastname: Gaffney-Stomberg
authors.affiliation: Military Nutrition Division, U.S. Army Research Institute of Environmental Medicine, Natick, MA 01760, USA. Andrew.J.Young.ctr@mail.mil.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Young
authors.affiliation: Military Nutrition Division, U.S. Army Research Institute of Environmental Medicine, Natick, MA 01760, USA. James.P.McClung8.civ@mail.mil.
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 02111, USA. Roger.Fielding@Tufts.edu.
authors.forename: Roger A
authors.initials: RA
authors.lastname: Fielding
authors.affiliation: Military Nutrition Division, U.S. Army Research Institute of Environmental Medicine, Natick, MA 01760, USA. Stefan.M.Pasiakos.civ@mail.mil.
authors.forename: Stefan M
authors.initials: SM
authors.lastname: Pasiakos
mesh_terms: D000818:Animals; D031204:Caloric Restriction; D004044:Dietary Proteins / Q000008:administration & dosage*; D015536:Down-Regulation; D050155:Lipogenesis / Q000502:physiology*; D008099:Liver / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000737:chemistry / Q000378:metabolism*
chemical_list: D004044:Dietary Proteins; D014280:Triglycerides
keywords: fatty acid synthase; fatty liver; insulin resistance; low carbohydrate diet