Department of Health and Kinesiology, Biology of Physical Activity Laboratory, Texas A&M University, College Station, TX, United States of America.
Department of Health and Kinesiology, Center for Translational Research in Aging & Longevity, Texas A&M University, College Station, TX, United States of America.
PLoS One. 2020 Jun 26;15(6):e0235095. doi: 10.1371/journal.pone.0235095. eCollection 2020.
Our previous studies suggest that physical activity (PA) levels are potentially regulated by endogenous metabolic mechanisms such as the vasodilatory roles of nitric oxide (NO) production via the precursor arginine (ARG) and ARG-related pathways. We assessed ARG metabolism and its precursors [citrulline (CIT), glutamine (GLN), glutamate (GLU), ornithine (ORN), and phenylalanine (PHE)] by measuring plasma concentration, whole-body production (WBP), de novo ARG and NO production, and clearance rates in previously classified low-active (LA) or high-active (HA) mice. We assessed LA (n = 23) and HA (n = 20) male mice by administering a stable isotope tracer pulse via jugular catheterization. We measured plasma enrichments via liquid chromatography tandem mass spectrometry (LC-MS/MS) and body compostion by echo-MRI. WBP, clearance rates, and de novo ARG and NO were calculated. Compared to LA mice, HA mice had lower plasma concentrations of GLU (71.1%; 36.8 ± 2.9 vs. 17.5 ± 1.7μM; p<0.0001), CIT (21%; 57.3 ± 2.3 vs. 46.4 ± 1.5μM; p = 0.0003), and ORN (40.1%; 55.4 ± 7.3 vs. 36.9 ± 2.6μM; p = 0.0241), but no differences for GLN, PHE, and ARG. However, HA mice had higher estimated NO production ratio (0.64 ± 0.08; p = 0.0197), higher WBP for CIT (21.8%, 8.6 ± 0.2 vs. 10.7 ± 0.3 nmol/g-lbm/min; p<0.0001), ARG (21.4%, 35.0 ± 0.6 vs. 43.4 ± 0.7 nmol/g-lbm/min; p<0.0001), PHE (7.6%, 23.8 ± 0.5 vs. 25.6 ± 0.5 nmol/g-lbm/min; p<0.0100), and lower GLU (78.5%; 9.4 ± 1.1 vs. 4.1 ± 1.6 nmol/g lbm/min; p = 0.0161). We observed no significant differences in WBP for GLN, ORN, PHE, or de novo ARG. We concluded that HA mice have an activated whole-body ARG pathway, which may be associated with regulating PA levels via increased NO production.
我们之前的研究表明，体力活动（PA）水平可能受到内源性代谢机制的调节，例如通过前体精氨酸（ARG）和 ARG 相关途径产生的血管扩张作用的一氧化氮（NO）。我们通过测量血浆浓度、全身产生（WBP）、从头 ARG 和 NO 产生以及先前分类的低活性（LA）或高活性（HA）小鼠中的清除率来评估 ARG 代谢及其前体[瓜氨酸（CIT）、谷氨酰胺（GLN）、谷氨酸（GLU）、鸟氨酸（ORN）和苯丙氨酸（PHE）]。我们通过颈内导管穿刺给予稳定同位素示踪脉冲来评估 LA（n = 23）和 HA（n = 20）雄性小鼠。我们通过回波-MRI 测量血浆富集物，并通过液体色谱串联质谱法（LC-MS/MS）测量身体组成。计算 WBP、清除率、从头 ARG 和 NO。与 LA 小鼠相比，HA 小鼠的 GLU 血浆浓度较低（71.1%；36.8 ± 2.9 与 17.5 ± 1.7μM；p<0.0001），CIT（21%；57.3 ± 2.3 与 46.4 ± 1.5μM；p = 0.0003）和 ORN（40.1%；55.4 ± 7.3 与 36.9 ± 2.6μM；p = 0.0241），但 GLN、PHE 和 ARG 没有差异。然而，HA 小鼠的估计 NO 产生比更高（0.64 ± 0.08；p = 0.0197），CIT 的 WBP 更高（21.8%，8.6 ± 0.2 与 10.7 ± 0.3 nmol/g-lbm/min；p<0.0001），ARG（21.4%，35.0 ± 0.6 与 43.4 ± 0.7 nmol/g-lbm/min；p<0.0001），PHE（7.6%，23.8 ± 0.5 与 25.6 ± 0.5 nmol/g-lbm/min；p<0.0100），GLU 更低（78.5%，9.4 ± 1.1 与 4.1 ± 1.6 nmol/g lbm/min；p = 0.0161）。我们没有观察到 GLN、ORN、PHE 或从头 ARG 的 WBP 有显著差异。我们得出结论，HA 小鼠具有激活的全身 ARG 途径，这可能与通过增加 NO 产生来调节 PA 水平有关。
