Metabolomic Associations with Serum Bone Turnover Markers.

Metabolomic Associations with Serum Bone Turnover Markers.
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DOI:
10.3390/nu12103161
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发表时间:
2020-10-16
期刊:
影响因子:
5.9
通讯作者:
Alvarez JA
Alvarez JA
中科院分区:
医学2区
文献类型:
--
作者:
Bellissimo MP;Roberts JL;Jones DP;Liu KH;Taibl KR;Uppal K;Weitzmann MN;Pacifici R;Drissi H;Ziegler TR;Alvarez JA

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骨是一种处于持续重塑状态的动态组织。骨转换标志物(BTM)、I型前胶原N端肽(P1NP)和I型胶原C端端肽(CTX)分别是骨形成和骨吸收的敏感指标。本研究使用超高分辨率代谢组学(HRM)来确定与成人骨吸收和形成标志物相关的血浆代谢途径和靶向代谢物。这项横断面临床研究包括34名成年人(19名女性,平均27.8岁),没有报告疾病,从美国大都市招募。用双抗体夹心法测定血清BTM水平。血浆HRM利用双柱液相色谱和质谱仪鉴定与BTMS相关的代谢物和代谢途径。与P1NP显著相关的代谢物(p<0.05)在与TCA循环、丙酮酸代谢和对能量产生重要的B维生素(例如烟酸、硫胺素)的代谢相关的途径中显著丰富。与P1NP相关的其他营养代谢途径是氨基酸(脯氨酸、精氨酸、谷氨酸)和维生素C代谢,它们对胶原蛋白的形成至关重要。与CTX水平相关的代谢物(p<0.05)在脂肪和脂肪酸β-氧化代谢途径以及脂溶微量营养素途径中富含,包括维生素D代谢、维生素E代谢和胆汁酸生物合成。P1NP和CTX与微生物组相关代谢产物显著相关(p<0.05)。与大量营养素相关的途径,包括脂肪、碳水化合物和氨基酸代谢,以及几种肠道微生物组衍生的代谢物,与BTMS显著相关。未来的研究应该将这里报道的代谢BTM与老龄化和临床人群的关系进行比较,以提供有针对性的治疗干预措施。
Bone is a dynamic tissue that is in a constant state of remodeling. Bone turnover markers (BTMs), procollagen type I N-terminal propeptide (P1NP) and C-terminal telopeptides of type I collagen (CTX), provide sensitive measures of bone formation and resorption, respectively. This study used ultra-high-resolution metabolomics (HRM) to determine plasma metabolic pathways and targeted metabolites related to the markers of bone resorption and formation in adults. This cross-sectional clinical study included 34 adults (19 females, mean 27.8 years), without reported illnesses, recruited from a US metropolitan area. Serum BTM levels were quantified by an ELISA. Plasma HRM utilized dual-column liquid chromatography and mass spectrometry to identify metabolites and metabolic pathways associated with BTMs. Metabolites significantly associated with P1NP (p < 0.05) were significantly enriched in pathways linked to the TCA cycle, pyruvate metabolism, and metabolism of B vitamins important for energy production (e.g., niacin, thiamin). Other nutrition-related metabolic pathways associated with P1NP were amino acid (proline, arginine, glutamate) and vitamin C metabolism, which are important for collagen formation. Metabolites associated with CTX levels (p < 0.05) were enriched within lipid and fatty acid beta-oxidation metabolic pathways, as well as fat-soluble micronutrient pathways including, vitamin D metabolism, vitamin E metabolism, and bile acid biosynthesis. P1NP and CTX were significantly related to microbiome-related metabolites (p < 0.05). Macronutrient-related pathways including lipid, carbohydrate, and amino acid metabolism, as well as several gut microbiome-derived metabolites were significantly related to BTMs. Future research should compare metabolism BTMs relationships reported here to aging and clinical populations to inform targeted therapeutic interventions.
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