title: Body composition and grip strength are improved in transgenic sickle mice fed a high-protein diet.
abstract: Key pathophysiology of sickle cell anaemia includes compensatory erythropoiesis, vascular injury and chronic inflammation, which divert amino acids from tissue deposition for growth/weight gain and muscle formation. We hypothesised that sickle mice maintained on an isoenergetic diet with a high percentage of energy derived from protein (35 %), as opposed to a standard diet with 20 % of energy derived from protein, would improve body composition, bone mass and grip strength. Male Berkeley transgenic sickle mice (S; n 8-12) were fed either 20 % (S20) or 35 % (S35) diets for 3 months. Grip strength (BIOSEB meter) and body composition (dual-energy X-ray absorptiometry scan) were measured. After 3 months, control mice had the highest bone mineral density (BMD) and bone mineral content (BMC) (P < 0·005). S35 mice had the largest increase in grip strength. A two-way ANOVA of change in grip strength (P = 0·043) attributed this difference to genotype (P = 0·025) and a trend in type of diet (P = 0·067). l-Arginine (l-Arg) supplementation of the 20 % diet was explored, as a possible mechanism for improvement obtained with the 35 % diet. Townes transgenic sickle mice (TS; n 6-9) received 0·8, 1·6, 3·2 or 6·4 % l-Arg based on the same protocol and outcome measures used for the S mice. TS mice fed 1·6 % l-Arg for 3 months (TS1.6) had the highest weight gain, BMD, BMC and lean body mass compared with other groups. TS3.2 mice showed significantly more improvement in grip strength than TS0·8 and TS1.6 mice (P < 0·05). In conclusion, the high-protein diet improved body composition and grip strength. Outcomes observed with TS1.6 and TS3.2 mice, respectively, confirm the hypothesis and reveal l-Arg as part of the mechanism.
authors.affiliation: Departments of Microbiology , Biochemistry and Immunology/Medicine , Morehouse School of Medicine , 720 Westview Drive SW , Atlanta , GA 30310 , USA ; University of Alabama at Birmingham , 1720 2nd Avenue South , Birmingham , AL 35294 , USA.
authors.forename: Patrice L
authors.initials: PL
authors.lastname: Capers
authors.affiliation: Departments of Microbiology , Biochemistry and Immunology/Medicine , Morehouse School of Medicine , 720 Westview Drive SW , Atlanta , GA 30310 , USA ; Medical University of South Carolina , 169 Ashley Avenue , SC 29403 , USA ; Aflac Cancer and Blood Disorder Center , Children's Healthcare of Atlanta , Emory University , 2015 Uppergate Drive , Atlanta , GA 30322 , USA.
authors.forename: Hyacinth I
authors.initials: HI
authors.lastname: Hyacinth
authors.affiliation: Departments of Microbiology , Biochemistry and Immunology/Medicine , Morehouse School of Medicine , 720 Westview Drive SW , Atlanta , GA 30310 , USA.
authors.forename: Shayla
authors.initials: S
authors.lastname: Cue
authors.affiliation: Aflac Cancer and Blood Disorder Center , Children's Healthcare of Atlanta , Emory University , 2015 Uppergate Drive , Atlanta , GA 30322 , USA.
authors.forename: Prasanthi
authors.initials: P
authors.lastname: Chappa
authors.affiliation: Division of Endocrinology and Metabolism and Lipids , Emory University School of Medicine , 101 Woodruff Circle , 1305 WMRB , Atlanta , GA 30322 , USA.
authors.forename: Tatyana
authors.initials: T
authors.lastname: Vikulina
authors.affiliation: Atlanta VA Medical Center , 1670 Clairmont Road , Decatur , GA 30033 , USA.
authors.forename: Susanne
authors.initials: S
authors.lastname: Roser-Page
authors.affiliation: Division of Endocrinology and Metabolism and Lipids , Emory University School of Medicine , 101 Woodruff Circle , 1305 WMRB , Atlanta , GA 30322 , USA ; Atlanta VA Medical Center , 1670 Clairmont Road , Decatur , GA 30033 , USA.
authors.forename: M Neale
authors.initials: MN
authors.lastname: Weitzmann
authors.affiliation: Aflac Cancer and Blood Disorder Center , Children's Healthcare of Atlanta , Emory University , 2015 Uppergate Drive , Atlanta , GA 30322 , USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Archer
authors.affiliation: Departments of Microbiology , Biochemistry and Immunology/Medicine , Morehouse School of Medicine , 720 Westview Drive SW , Atlanta , GA 30310 , USA.
authors.forename: Gale W
authors.initials: GW
authors.lastname: Newman
authors.affiliation: Departments of Microbiology , Biochemistry and Immunology/Medicine , Morehouse School of Medicine , 720 Westview Drive SW , Atlanta , GA 30310 , USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Quarshie
authors.affiliation: Departments of Microbiology , Biochemistry and Immunology/Medicine , Morehouse School of Medicine , 720 Westview Drive SW , Atlanta , GA 30310 , USA.
authors.forename: Jonathan K
authors.initials: JK
authors.lastname: Stiles
authors.affiliation: Departments of Microbiology , Biochemistry and Immunology/Medicine , Morehouse School of Medicine , 720 Westview Drive SW , Atlanta , GA 30310 , USA.
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Hibbert
keywords: BMC, bone mineral content; BMD, bone mineral density; Body composition; C, C57BL/6 (control) mice; C20, control mice fed diet supplying 20 % energy from protein; C35, control mice fed diet supplying 35 % energy from protein; DXA, dual-energy X-ray absorptiometry; Grip strength; High-protein diet; LBM, lean body mass; S, Berkeley transgenic sickle mice; S20, Berkeley sickle mice fed diet supplying 20 % energy from protein; S35, Berkeley sickle mice fed diet supplying 35 % energy from protein; SCA, sickle cell anaemia; Sickle cell disease; TS, Townes sickle mice; TS0.8, Townes sickle mice fed 0·8 % l-Arg diet; TS1.6, Townes sickle mice fed 1·6 % l-Arg diet; TS3.2, Townes sickle mice fed 3·2 % l-Arg diet; TS6.4, Townes sickle mice fed 6·4 % l-Arg diet; l-Arg, l-arginine