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, 3 (10), e10224
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Monosodium Glutamate Supplementation Improves Bone Status in Mice Under Moderate Protein Restriction

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Monosodium Glutamate Supplementation Improves Bone Status in Mice Under Moderate Protein Restriction

Anne Blais et al. JBMR Plus.

Abstract

Adequate protein intake during development is critical to ensure optimal bone gain and to attain a higher peak bone mass later. Using a mild protein restriction model in Balb/C mice consuming 6% of their total energy intake as soy protein (LP-SOY)-for which we observed a significantly lower femoral cortical thickness, bone volume, trabecular number, and thickness reduction-we evaluated the effects of monosodium glutamate (MSG) supplementation at different concentrations (0.5, 1, 5, 10, and 20 g/kg of diet) on bone characteristics in LP-SOY-fed mice. After 6 and 12 weeks, LP-SOY-fed mice had lower BMD and reduced body weight related to lower lean mass, which was associated with a reduced IGF-1 level. The negative effect of the LP-SOY diet on BMD correlated with impaired bone formation. MSG supplementation, at 5, 10, and 20 g/kg of diet, and PTH injection, used as a positive control, were able to improve BMD and to increase osteoblast activity markers (P1NP and osteocalcin), as well as glutamine plasma concentration. An analysis of bone microarchitecture found that cortical bone was less sensitive to protein restriction than trabecular bone, and that MSG ingestion was able to preserve bone quality through an increase of collagen synthesis, although it did not allow normal bone growth. Our study reinforces the view that glutamate can act as a functional amino acid for bone physiology and support clinical investigation of glutamate supplementation in adults characterized by poor bone status, notably as a result of insufficient protein intake. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Keywords: BONE TURNOVER; BONE μCT; COLLAGEN SYNTHESIS; DIETARY PROTEIN RESTRICTION; MICE MODEL; MONOSODIUM GLUTAMATE.

Figures

Figure 1
Figure 1
Effect of restricted protein diet with increasing amounts of monosodium glutamate (MSG) on body weight and body composition. The mice were fed for 12 weeks with either normal protein (NP) diet (20% soy protein) or with a 6% soy protein diet (low protein [LP]), without or with increasing amounts of MSG, and for the positive anabolic control with 1‐34 PTH injection (LP + PTH). Body and organs were weighed immediately after sacrifice. (A) Body weight. (B) Carcass weight. (C) Total fat mass. (D) Uterus weight. (E) Kidney weight. (F) Liver weight. Data are presented as box and whiskers, n = 12 per group. Each group is compared with the others by a one‐way ANOVA on repeated measures followed by a Tukey post hoc test. Means that are significantly different (p < 0.05) according to the Tukey multiple comparison test have different letters.
Figure 2
Figure 2
Effect of restricted protein diet with increasing amounts of monosodium glutamate (MSG) on whole body, femoral and lumbar spine BMD. The mice were fed for 12 weeks with either normal protein (NP) diet (20% soy protein) or with a 6% soy protein diet (low protein [LP]) without or with increasing amounts of MSG, and for the positive anabolic control with 1‐34 PTH injection (LP + PTH). (A) Evolution of whole‐body BMD as function of time. BMD gain was compared with the T0 values. Values are expressed as mean ± SD, n = 12. (B) Effect after 12 weeks of treatment with increasing amounts of MSG or PTH on femoral BMD. (C) Effects after 12‐week treatment with increasing amounts of MSG or PTH on lumbar spine BMD. Data are presented as box and whiskers for femoral and lumbar spine BMD, with n = 12 per group. Each group is compared with the others by a one‐way ANOVA on repeated measures followed by a Tukey post hoc test. Means that are significantly different (p < 0.05) according to the Tukey multiple comparison test have different letters.
Figure 3
Figure 3
Effect of restricted protein diet with increasing amounts of monosodium glutamate (MSG) on IGF‐1, CTX, PINP, and osteocalcin plasma concentrations. The mice were fed for 12 weeks with either normal protein (NP) diet (20% soy protein) or with a 6% soy protein diet (low protein [LP]) without or with increasing amounts of MSG, and for the positive anabolic control, with 1‐34 PTH injection (LP + PTH). Then IGF‐1 (A) and the bone remodeling markers CTX (B), PINP (C), and osteocalcin (D) were measured in the plasma. Data are presented as box and whiskers, n = 12 per group. Each group is compared with the others by a one‐way ANOVA on repeated measures followed by a Tukey post hoc test. Means that are significantly different (p < 0.05) according to the Tukey multiple comparison test have different letters.
Figure 4
Figure 4
Effect of restricted protein diet with increasing amounts of monosodium glutamate (MSG) on trabecular bone. The mice were fed for 12 weeks with either normal protein (NP) diet (20% soy protein) or with a 6% soy protein diet (low protein [LP]) without or with increasing amounts of MSG, and for the positive anabolic control, with 1‐34 PTH injection (LP + PTH). Then the bone microarchitecture was determined. Typical and representative examples of ex vivo μCT reconstruction of trabecular bone in different conditions (upper panel) and in lower panel comparison of (B) the bone volume to the total volume of the region of interest (BV/TV), (C) trabecular thickness (Tb.Th), and (D) trabecular number (Tb.N) in different conditions.
Figure 5
Figure 5
Effect of restricted protein diet with increasing amounts of monosodium glutamate (MSG) on cortical bone. The mice were fed for 12 weeks with either normal protein (NP) diet (20% soy protein) or with a 6% soy protein diet (low protein [LP]) without or with increasing amounts of MSG, and for the positive anabolic control, with 1‐34 PTH injection (LP + PTH). Then the bone microarchitecture was determined. Typical and representative examples of ex vivo μCT reconstruction of cortical bone in different conditions (upper panel) and in lower panel comparison of (B) cortical thickness, (C) cortical porosity (Ct.Po), and (D) bone area (B.Ar) in different conditions.
Figure 6
Figure 6
Effect of restricted protein diet with increasing amounts of monosodium glutamate (MSG) on bone characteristics. The mice were fed for 12 weeks with either normal (NP) protein diet (20% soy protein) or with a 6% soy protein diet (low protein [LP]) without or with increasing amounts of MSG, and for the positive anabolic control with 1‐34 PTH injection (LP + PTH). (A) Femur length. (B) Femur dry weight. (C) Ash weight. (D) Protein weight. Data are presented as box and whiskers for femoral and lumbar spine BMD, with n = 12 per group. Each group is compared with the others by a one‐way ANOVA on repeated measures followed by a Tukey post hoc test. Means that are significantly different (p < 0.05) according to the Tukey multiple comparison test have different letters.

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