l-Cysteine and Vitamin D Co-Supplementation Alleviates Markers of Musculoskeletal Disorders in Vitamin D-Deficient High-Fat Diet-Fed Mice.

l-Cysteine and Vitamin D Co-Supplementation Alleviates Markers of Musculoskeletal Disorders in Vitamin D-Deficient High-Fat Diet-Fed Mice.
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DOI:
10.3390/nu12113406
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发表时间:
2020-11-06
期刊:
影响因子:
5.9
通讯作者:
Jain SK
Jain SK
中科院分区:
医学2区
文献类型:
--
作者:
Parsanathan R;Achari AE;Manna P;Jain SK

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维生素D(VD)缺乏与肌肉骨骼疾病有关。本研究检查了L-半胱氨酸(LC)和VD的共同补充是否优于单独使用LC或VD缓解VD缺乏高脂饮食(HFD-VD-)喂养小鼠骨骼肌中的肌肉骨骼平衡障碍。小鼠喂食健康饮食或HFD;对于VD缺陷动物,小鼠维持HFD-VD饮食(16周);前8周后,HFD-VD饮食喂养的小鼠通过经口灌胃补充LC、单独VD或相同剂量的LC + VD另外8周。盐水和橄榄油作为对照。将肌管暴露于高糖、棕榈酸、单核细胞趋化蛋白1(MCP-1)和肿瘤坏死因子(TNF)中,以模拟体内微环境。在体外缺陷的谷胱甘肽和硫化氢诱导GCLC和CSE基因敲低。使用qRT-PCR分析生物标志物(肌源性:MyoD、Mef 2c、Csrp 3;肌营养不良:Atrogin 1、Murf 1和Myostatin;骨建模和重塑:RANK、RANKL、OPG)的相对基因表达。与单独补充LC或VD相比,与LC + VD联合补充对生肌标志物和OPG的基因表达显示出有益影响,但减少了营养不良标志物RANK/RANKL。用谷胱甘肽(GSH)前体处理的体外肌管也显示出对OPG和肌生成基因的积极作用,并抑制RANK/RANKL和肌肉营养不良标志物。该研究揭示,在HFD-VD喂养的小鼠中,LC与VD的共补充显著地改善了骨骼肌中的肌肉骨骼疾病的标志物,优于LC或VD的单一疗法。
Vitamin D (VD) deficiency is associated with musculoskeletal disorders. This study examines whether co-supplementation of l-cysteine (LC) and VD is better than monotherapy with LC or VD at alleviating musculoskeletal dyshomeostasis in the skeletal muscle of VD-deficient high-fat diet (HFD-VD-) fed mice. Mice were fed a healthy diet or an HFD; for VD-deficient animals, the mice were maintained on a HFD-VD-diet (16 weeks); after the first 8 weeks, the HFD-VD-diet-fed mice were supplemented for another 8 weeks with LC, VD-alone, or the same doses of LC + VD by oral gavage. Saline and olive oil served as controls. Myotubes were exposed with high-glucose, palmitate, Monocyte Chemoattractant Protein 1 (MCP-1), and Tumor Necrosis Factor (TNF), to mimic the in vivo microenvironment. In vitro deficiencies of glutathione and hydrogen sulfide were induced by knockdown of GCLC and CSE genes. Relative gene expression of biomarkers (myogenic: MyoD, Mef2c, Csrp3; muscle dystrophy: Atrogin1, Murf1, and Myostatin; bone modeling and remodeling: RANK, RANKL, OPG) were analyzed using qRT-PCR. Co-supplementatoin with LC + VD showed beneficial effects on gene expression of myogenic markers and OPG but reduced markers of dystrophy, RANK/RANKL in comparison to LC or VD alone-supplementation. In vitro myotubes treated with glutathione (GSH) precursors also showed a positive effect on OPG and the myogenesis genes, and inhibited RANK/RANKL and muscle-dystrophy markers. This study reveals that the co-supplementation of LC with VD significantly alleviates the markers of musculoskeletal disorders in the skeletal muscle better than monotherapy with LC or VD in HFD-VD-fed mice.
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