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Untargeted metabolomics identifies the potential role of monocarboxylate transporter 6 (MCT6/SLC16A5) in lipid and amino acid metabolism pathways
Pharmacology Research & Perspectives ( IF 2.9 ) Pub Date : 2022-04-24 , DOI: 10.1002/prp2.944
Tianjing Ren 1 , Robert S Jones 2 , Marilyn E Morris 1
Pharmacology Research & Perspectives ( IF 2.9 ) Pub Date : 2022-04-24 , DOI: 10.1002/prp2.944
Tianjing Ren 1 , Robert S Jones 2 , Marilyn E Morris 1
Affiliation
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Monocarboxylate transporter 6 (MCT6; SLC16A5) is an orphan transporter protein with expression in multiple tissues. The endogenous function of MCT6 related to human health and disease remains unknown. Our previous transcriptomic and proteomic analyses in Mct6 knockout (KO) mice suggested that MCT6 may play a role in lipid and glucose homeostasis, but additional evidence is required. Thus, the objective of this study was to further explore the impact of MCT6 on metabolic function using untargeted metabolomic analysis in Mct6 KO mice. The plasma from male and female mice and livers from male mice were submitted for global metabolomics analysis to assess the relative changes in endogenous small molecules across the liver and systemic circulation associated with absence of Mct6. More than 782 compounds were detected with 101 and 51 metabolites significantly changed in plasma of male and female mice, respectively, and 100 metabolites significantly changed in the livers of male mice (p < .05). Significant perturbations in lipid metabolism were annotated in the plasma and liver metabolome, with additional alterations in the amino acid metabolism pathway in plasma samples from male and female mice. Elevated lipid diacylglycerol and altered fatty acid metabolite concentrations were found in liver and plasma samples of male Mct6 KO mice. Significant reduction of N-terminal acetylated amino acids was found in plasma samples of male and female Mct6 KO mice. In summary, the present study confirmed the significant role of MCT6 in lipid and amino acid homeostasis, suggesting its contribution in metabolic diseases.
中文翻译：
非靶向代谢组学鉴定了单羧酸转运蛋白 6 (MCT6/SLC16A5) 在脂质和氨基酸代谢途径中的潜在作用
单羧酸转运蛋白 6 (MCT6; SLC16A5 ) 是一种孤儿转运蛋白，在多种组织中表达。 MCT6与人类健康和疾病相关的内源性功能仍不清楚。我们之前对 Mct6 敲除 (KO) 小鼠进行的转录组学和蛋白质组学分析表明，MCT6 可能在脂质和葡萄糖稳态中发挥作用，但需要更多证据。因此，本研究的目的是利用 Mct6 KO 小鼠的非靶向代谢组学分析进一步探讨 MCT6 对代谢功能的影响。将雄性和雌性小鼠的血浆以及雄性小鼠的肝脏提交进行整体代谢组学分析，以评估与 Mct6 缺失相关的肝脏和全身循环中内源性小分子的相对变化。检测到超过 782 种化合物，其中雄性和雌性小鼠血浆中分别有 101 和 51 种代谢物显着变化，雄性小鼠肝脏中有 100 种代谢物显着变化 ( p < .05)。血浆和肝脏代谢组中脂质代谢的显着扰动被注释，雄性和雌性小鼠血浆样本中的氨基酸代谢途径也发生了额外的改变。在雄性 Mct6 KO 小鼠的肝脏和血浆样本中发现脂质二酰甘油升高和脂肪酸代谢物浓度改变。在雄性和雌性 Mct6 KO 小鼠血浆样本中发现 N 末端乙酰化氨基酸显着减少。总之，本研究证实了 MCT6 在脂质和氨基酸稳态中的重要作用，表明其在代谢疾病中的贡献。
更新日期：2022-04-26
中文翻译：
非靶向代谢组学鉴定了单羧酸转运蛋白 6 (MCT6/SLC16A5) 在脂质和氨基酸代谢途径中的潜在作用
单羧酸转运蛋白 6 (MCT6; SLC16A5 ) 是一种孤儿转运蛋白，在多种组织中表达。 MCT6与人类健康和疾病相关的内源性功能仍不清楚。我们之前对 Mct6 敲除 (KO) 小鼠进行的转录组学和蛋白质组学分析表明，MCT6 可能在脂质和葡萄糖稳态中发挥作用，但需要更多证据。因此，本研究的目的是利用 Mct6 KO 小鼠的非靶向代谢组学分析进一步探讨 MCT6 对代谢功能的影响。将雄性和雌性小鼠的血浆以及雄性小鼠的肝脏提交进行整体代谢组学分析，以评估与 Mct6 缺失相关的肝脏和全身循环中内源性小分子的相对变化。检测到超过 782 种化合物，其中雄性和雌性小鼠血浆中分别有 101 和 51 种代谢物显着变化，雄性小鼠肝脏中有 100 种代谢物显着变化 ( p < .05)。血浆和肝脏代谢组中脂质代谢的显着扰动被注释，雄性和雌性小鼠血浆样本中的氨基酸代谢途径也发生了额外的改变。在雄性 Mct6 KO 小鼠的肝脏和血浆样本中发现脂质二酰甘油升高和脂肪酸代谢物浓度改变。在雄性和雌性 Mct6 KO 小鼠血浆样本中发现 N 末端乙酰化氨基酸显着减少。总之，本研究证实了 MCT6 在脂质和氨基酸稳态中的重要作用，表明其在代谢疾病中的贡献。
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