Plasma carnosine, but not muscle carnosine, attenuates high-fat diet-induced metabolic stress
Plasma carnosine, but not muscle carnosine, attenuates high-fat diet-induced metabolic stress
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DOI：
10.1139/apnm-2015-0042
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发表时间：
2015-09-01
影响因子：
3.4
通讯作者：
Derave, Wim
中科院分区：
文献类型：
--
作者：
Stegen, Sanne;Stegen, Bram;Derave, Wim
越来越多的体内证据表明，二肽肌肽在代谢性疾病中具有保护作用。一个关键的未回答的问题是它的作用部位是组织还是血浆。在高脂肪饮食大鼠模型中使用口服肌肽对比β-丙氨酸补充来研究这一点。36只雄性Sprague-Dawley大鼠接受对照饮食（CON）、高脂肪饮食（HF; 60%的能量来自脂肪）、具有1.8%肌肽的HF饮食（HFcar）或具有1% β-丙氨酸的HF饮食（HFba），因为β-丙氨酸可以增加肌肉肌肽而不增加血浆肌肽。在骨骼肌和血液中测定胰岛素敏感性、炎症信号传导和脂氧化应激。在一项初步研究中，收集了尿液。3个HF组明显比CON组重。HFcar和HFba组中肌肉肌肽浓度同样增加，而仅在HFcar组中检测到升高的血浆肌肽水平和肌肽-4-羟基-2-壬烯醛加合物。HF大鼠中升高的血浆和尿N-羟甲基赖氨酸在HFcar组中降低了约50%，但在HFba组中未降低。同样，与HF大鼠相比，HFcar组中诱导型一氧化氮合酶mRNA降低了47%（p < 0.05），但HFba组中没有。我们的结论是，血浆肌肽，但不是肌肉肌肽，参与防止早期阶段的脂肪氧化在循环和炎症信号在肌肉中的大鼠。
There is growing in vivo evidence that the dipeptide carnosine has protective effects in metabolic diseases. A critical unanswered question is whether its site of action is tissues or plasma. This was investigated using oral carnosine versus beta-alanine supplementation in a high-fat diet rat model. Thirty-six male Sprague-Dawley rats received a control diet (CON), a high-fat diet (HF; 60% of energy from fat), the HF diet with 1.8% carnosine (HFcar), or the HF diet with 1% beta-alanine (HFba), as beta-alanine can increase muscle carnosine without increasing plasma carnosine. Insulin sensitivity, inflammatory signaling, and lipoxidative stress were determined in skeletal muscle and blood. In a pilot study, urine was collected. The 3 HF groups were significantly heavier than the CON group. Muscle carnosine concentrations increased equally in the HFcar and HFba groups, while elevated plasma carnosine levels and carnosine-4-hydroxy-2-nonenal adducts were detected only in the HFcar group. Elevated plasma and urine N-epsilon-(carboxymethyl)lysine in HF rats was reduced by similar to 50% in the HFcar group but not in the HFba group. Likewise, inducible nitric oxide synthase mRNA was decreased by 47% (p < 0.05) in the HFcar group, but not in the HFba group, compared with HF rats. We conclude that plasma carnosine, but not muscle carnosine, is involved in preventing early-stage lipoxidation in the circulation and inflammatory signaling in the muscle of rats.