Dimethylguanidino Valeric Acid (DMGV) is a marker of fatty liver disease, incident coronary artery disease, cardiovascular mortality, and incident diabetes. Recently, it was reported that circulating DMGV levels correlated positively with consumption of sugary beverages and negatively with intake of fruits and vegetables, in three Swedish community-based cohorts. Here, we validate these results in the Framingham Heart Study Third Generation Cohort. Furthermore, in mice, diets rich in sucrose or fat significantly increased plasma DMGV concentrations. DMGV is the product of metabolism of asymmetric dimethylarginine (ADMA) by the hepatic enzyme AGXT2. ADMA can also be metabolized to citrulline by the cytoplasmic enzyme DDAH1. We report that a high sucrose diet induced conversion of ADMA exclusively into DMGV (supporting the relationship with sugary beverage intake in humans), while a high-fat diet promoted conversion of ADMA to both DMGV and citrulline. On the contrary, replacing dietary native starch with high fiber-resistant starch increased ADMA concentrations and induced its conversion to citrulline, without altering DMGV concentrations. In a cohort of obese non-diabetic adults, circulating DMGV concentrations increased and ADMA levels decreased in those with either liver or muscle insulin resistance. This was similar to changes in DMGV and ADMA concentrations found in mice fed a high-sucrose diet. Sucrose is a disaccharide of glucose and fructose. Compared with glucose, incubation of hepatocytes with fructose significantly increased DMGV production. Overall, we provide a comprehensive picture of the dietary determinants of DMGV levels and its association with insulin resistance.

中文翻译：

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代谢物二甲基胍基戊酸的营养和代谢调节：心脏代谢疾病的早期标志物。

二甲基胍基戊酸 (DMGV) 是脂肪肝、冠状动脉疾病、心血管死亡率和糖尿病的标志物。最近，据报道，在三个瑞典社区队列中，循环 DMGV 水平与含糖饮料的消费呈正相关，与水果和蔬菜的摄入呈负相关。在这里，我们在弗雷明汉心脏研究第三代队列中验证了这些结果。此外，在小鼠中，富含蔗糖或脂肪的饮食显着增加了血浆 DMGV 浓度。DMGV 是肝酶 AGXT2 代谢不对称二甲基精氨酸 (ADMA) 的产物。ADMA 也可以通过细胞质酶 DDAH1 代谢为瓜氨酸。我们报告说，高蔗糖饮食仅诱导 ADMA 转化为 DMGV（支持与人类含糖饮料摄入量的关系），而高脂肪饮食促进 ADMA 转化为 DMGV 和瓜氨酸。相反，用高纤维抗性淀粉代替膳食天然淀粉会增加 ADMA 浓度并诱导其转化为瓜氨酸，而不会改变 DMGV 浓度。在一组肥胖的非糖尿病成人中，有肝脏或肌肉胰岛素抵抗的人的循环 DMGV 浓度增加，而 ADMA 水平降低。这类似于在喂食高蔗糖饮食的小鼠中发现的 DMGV 和 ADMA 浓度的变化。蔗糖是葡萄糖和果糖的二糖。与葡萄糖相比，用果糖孵育肝细胞显着增加了 DMGV 的产生。总体，