Integrative Physiology and Metabolism Laboratory, Department of Physiology, Monash University, Clayton, Victoria, Australia.
PLoS One. 2013 Sep 6;8(9):e72449. doi: 10.1371/journal.pone.0072449. eCollection 2013.
Dysfunctional lipid metabolism is a hallmark of obesity and insulin resistance and a risk factor for various cardiovascular and metabolic complications. In addition to the well known increase in plasma triglycerides and free fatty acids, recent work in humans and rodents has shown that obesity is associated with elevations in the bioactive class of sphingolipids known as ceramides. However, in obesity little is known about the plasma concentrations of sphinogsine-1-phosphate (S1P), the breakdown product of ceramide, which is an important signaling molecule in mammalian biology. Therefore, the purpose of this study was to examine the impact of obesity on circulating S1P concentration and its relationship with markers of glucose metabolism and insulin sensitivity.
METHODOLOGY/PRINCIPAL FINDINGS: Plasma S1P levels were determined in high-fat diet (HFD)-induced and genetically obese (ob/ob) mice along with obese humans. Circulating S1P was elevated in both obese mouse models and in obese humans compared with lean healthy controls. Furthermore, in humans, plasma S1P positively correlated with total body fat percentage, body mass index (BMI), waist circumference, fasting insulin, HOMA-IR, HbA1c (%), total and LDL cholesterol. In addition, fasting increased plasma S1P levels in lean healthy mice.
We show that elevations in plasma S1P are a feature of both human and rodent obesity and correlate with metabolic abnormalities such as adiposity and insulin resistance.
脂代谢功能障碍是肥胖和胰岛素抵抗的标志，也是各种心血管和代谢并发症的危险因素。除了众所周知的血浆甘油三酯和游离脂肪酸增加外，最近在人类和啮齿动物中的研究表明，肥胖与生物活性鞘脂类（称为神经酰胺）的升高有关。然而，在肥胖症中，关于神经酰胺分解产物鞘氨醇-1-磷酸（S1P）的血浆浓度知之甚少，而 S1P 是哺乳动物生物学中的一种重要信号分子。因此，本研究的目的是研究肥胖对循环 S1P 浓度的影响及其与葡萄糖代谢和胰岛素敏感性标志物的关系。
方法/主要发现：测定高脂肪饮食（HFD）诱导的肥胖和遗传性肥胖（ob/ob）小鼠以及肥胖人群的血浆 S1P 水平。与瘦健康对照组相比，两种肥胖小鼠模型和肥胖人群的循环 S1P 水平均升高。此外，在人类中，血浆 S1P 与体脂肪百分比、体重指数（BMI）、腰围、空腹胰岛素、HOMA-IR、HbA1c（%）、总胆固醇和 LDL 胆固醇呈正相关。此外，在瘦健康小鼠中，空腹会增加血浆 S1P 水平。
我们表明，血浆 S1P 的升高是人类和啮齿动物肥胖的特征，并与肥胖和胰岛素抵抗等代谢异常相关。
