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.
Highlights
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
The objective of the present study was to determine the effect of a high-protein diet and increased L-Arg on body composition and grip strength in sickle mice
It was our hypothesis that both a high-protein diet and increased L-Arg would provide additional nutrients that sickle mice might need to improve a characteristically slower rate of weight gain[11], which would probably result in inadequate lean body mass (LBM) and less strength for the use of limbs
Summary
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. The functions of L-Arg are many, including growth and muscle development[6,7,8], making it a semiessential amino acid based on the stage of development Both mice[9,10,11] and human subjects[12,13] with sickle cell disease typically have low Arg levels associated with vasoconstriction and several attendant complications, including acute chest syndrome. Children with SCA have significantly lower body weight, height, bone mineral density (BMD) and bone mineral content (BMC) compared with healthy controls[22,23,24] These processes increase the nutritional requirements for SCA patients, making an otherwise normal dietary intake insufficient[25] to maintain growth and development, as often observed among SCA patients[20,26]
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