Systematic metabolomic studies identified adult adiposity biomarkers with acetylglycine associated with fat loss in vivo.
Systematic metabolomic studies identified adult adiposity biomarkers with acetylglycine associated with fat loss in vivo.
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DOI：
10.3389/fmolb.2023.1166333
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发表时间：
2023
影响因子：
5
通讯作者：
中科院分区：
文献类型：
--
作者：
肥胖与各种不良健康结果有关。体脂分布被认为是肥胖对健康产生负面影响的一个重要因素。虽然代谢组学研究，主要集中在身体质量指数（BMI）和腰围，探讨了肥胖的发展中涉及的生物学机制，这些代理复合措施是不准确的，不能反映BF分布，因此可能会阻碍准确评估代谢改变和代谢紊乱的个体之间的差异风险呈现不同的肥胖全身。因此，代谢产物和BF之间的确切关系仍有待阐明。在这里，我们的目的是研究协会的代谢产物和代谢途径与BF性状，反映BF分布。我们对517名中国女性进行了系统的非靶向血清代谢物分析和双能X线吸收法（DXA）全身脂肪扫描。我们联合分析了DXA衍生的四种BF表型，以检测交叉表型代谢物相关性并优先考虑重要的代谢组学因素。基于拓扑的途径分析被用来确定重要的BF相关的生物过程。最后，我们通过两个独立的队列研究了不同性别和种族的BF相关候选代谢物与BF性状的关系。乙酰甘氨酸是最显著的发现，通过对各种饮食诱导的肥胖（DIO）小鼠的体内研究，验证了其抗肥胖作用。发现18种代谢产物和14种途径与BF表型相关。在不同性别和种族中验证了6种代谢产物。在人和DIO小鼠中观察到乙酰甘氨酸的抗肥胖作用是高度稳健和可推广的。这些研究结果表明，与BF分布模式和几个生物学途径，可能有助于肥胖和肥胖相关疾病的病因，预防和干预的代谢物的重要性。乙酰甘氨酸在未来的研究中被强调为预防过度肥胖的潜在治疗候选者。
Obesity is associated with various adverse health outcomes. Body fat (BF) distribution is recognized as an important factor of negative health consequences of obesity. Although metabolomics studies, mainly focused on body mass index (BMI) and waist circumference, have explored the biological mechanisms involved in the development of obesity, these proxy composite measures are not accurate and cannot reflect BF distribution, and thus may hinder accurate assessment of metabolic alterations and differential risk of metabolic disorders among individuals presenting adiposity differently throughout the body. Thus, the exact relations between metabolites and BF remain to be elucidated. Here, we aim to examine the associations of metabolites and metabolic pathways with BF traits which reflect BF distribution. We performed systematic untargeted serum metabolite profiling and dual-energy X-ray absorptiometry (DXA) whole body fat scan for 517 Chinese women. We jointly analyzed DXA-derived four BF phenotypes to detect cross-phenotype metabolite associations and to prioritize important metabolomic factors. Topology-based pathway analysis was used to identify important BF-related biological processes. Finally, we explored the relationships of the identified BF-related candidate metabolites with BF traits in different sex and ethnicity through two independent cohorts. Acetylglycine, the top distinguished finding, was validated for its obesity resistance effect through in vivo studies of various diet-induced obese (DIO) mice. Eighteen metabolites and fourteen pathways were discovered to be associated with BF phenotypes. Six of the metabolites were validated in varying sex and ethnicity. The obesity-resistant effects of acetylglycine were observed to be highly robust and generalizable in both human and DIO mice. These findings demonstrate the importance of metabolites associated with BF distribution patterns and several biological pathways that may contribute to obesity and obesity-related disease etiology, prevention, and intervention. Acetylglycine is highlighted as a potential therapeutic candidate for preventing excessive adiposity in future studies.
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影响因子：
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作者：
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通讯作者：
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Pietilainen, Kirsi H.
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Hjelmesæth J;Røislien J;Nordstrand N;Hofsø D;Hager H;Hartmann A
通讯作者：
Hartmann A