Type 2 Diabetes Associated Changes in the Plasma Non-Esterified Fatty Acids, Oxylipins and Endocannabinoids
Type 2 Diabetes Associated Changes in the Plasma Non-Esterified Fatty Acids, Oxylipins and Endocannabinoids
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DOI：
10.1371/journal.pone.0048852
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发表时间：
2012-11-08
期刊：
影响因子：
3.7
通讯作者：
Newman, John W.
中科院分区：
文献类型：
--
作者：
Grapov, Dmitry;Adams, Sean H.;Newman, John W.
2型糖尿病对代谢有深远的影响，可以在血浆中检测到。虽然糖尿病患者循环中非酯化脂肪酸（NEFA）的增加已得到充分描述，但对信号脂质的影响却很少受到关注。氧脂素和内源性大麻素是一类具有生物活性的脂肪酸代谢物，具有许多结构成员，通过自分泌、旁分泌和内分泌机制影响胰岛素信号传导、脂肪功能和炎症。为了将糖尿病相关的血浆NEFA和信号脂质的变化联系起来，我们定量靶向年龄和体重指数匹配的超重至肥胖、非糖尿病（n = 12）和2型糖尿病（n = 43）非裔美国妇女中的>150种血浆脂质组成分。糖尿病相关的NEFA模式表明类似于60%的固醇-CoA去饱和酶活性增加和类似于40%的极长链多不饱和脂肪酸链缩短减少，模式先前与非酒精性脂肪肝疾病的发展相关。此外，18碳多不饱和脂肪酸的环氧化物和酮在糖尿病中升高>80%，并且与NEFA的变化密切相关，这与它们在脂肪分解期间的释放一致。内源性大麻素的行为不同类糖尿病增加了一系列的N-酰基乙醇酰胺，这是正相关的促炎性5-脂氧合酶衍生的代谢产物，而单酰基甘油与体重呈负相关。这些结果清楚地表明，糖尿病不仅导致血浆NEFA的增加，而且以反映这种病理状态的生物化学和生理学变化的方式改变血浆脂质组学特征，其独立于肥胖相关的变化。引文：Grapov D，亚当斯SH，彼得森TL，Garvey WT，纽曼JW（2012）2型糖尿病相关的血浆非酯化脂肪酸、氧脂素和内源性大麻素的变化。PLoS ONE 7（11）：e48852. doi：10.1371/journal.pone.0048852
Type 2 diabetes has profound effects on metabolism that can be detected in plasma. While increases in circulating non-esterified fatty acids (NEFA) are well-described in diabetes, effects on signaling lipids have received little attention. Oxylipins and endocannabinoids are classes of bioactive fatty acid metabolites with many structural members that influence insulin signaling, adipose function and inflammation through autocrine, paracrine and endocrine mechanisms. To link diabetes-associated changes in plasma NEFA and signaling lipids, we quantitatively targeted >150 plasma lipidome components in age- and body mass index-matched, overweight to obese, non-diabetic (n = 12) and type 2 diabetic (n = 43) African-American women. Diabetes related NEFA patterns indicated similar to 60% increase in steroyl-CoA desaturase activity and similar to 40% decrease in very long chain polyunsaturated fatty acid chain shortening, patterns previously associated with the development of nonalcoholic fatty liver disease. Further, epoxides and ketones of eighteen carbon polyunsaturated fatty acids were elevated >80% in diabetes and strongly correlated with changes in NEFA, consistent with their liberation during adipose lipolysis. Endocannabinoid behavior differed by class with diabetes increasing an array of N-acylethanolamides which were positively correlated with pro-inflammatory 5-lipooxygenase-derived metabolites, while monoacylglycerols were negatively correlated with body mass. These results clearly show that diabetes not only results in an increase in plasma NEFA, but shifts the plasma lipidomic profiles in ways that reflect the biochemical and physiological changes of this pathological state which are independent of obesity associated changes. Citation: Grapov D, Adams SH, Pedersen TL, Garvey WT, Newman JW (2012) Type 2 Diabetes Associated Changes in the Plasma Non-Esterified Fatty Acids, Oxylipins and Endocannabinoids. PLoS ONE 7(11): e48852. doi: 10.1371/journal.pone.0048852