Skeletal muscle ceramide species in men with abdominal obesity
Skeletal muscle ceramide species in men with abdominal obesity
复制标题
DOI：
10.1007/s12603-014-0548-7
复制
发表时间：
2015-04-01
影响因子：
5.8
通讯作者：
Bunout, D.
中科院分区：
文献类型：
--
作者：
de la Maza, M. P.;Rodriguez, J. M.;Bunout, D.
背景：肥胖是糖尿病及其后果的危险因素，包括加速衰老和死亡。潜在的因素可能是某些脂质部分的积累，例如肌肉组织中的神经酰胺（CER）和二酰基甘油（DAG），已知其促进胰岛素抵抗（IR），诱导炎症和氧化损伤，最终改变肌肉功能。目的：首先，研究身体成分和年龄（自变量）与骨骼肌脂质种类积累、氧化损伤和力量的关系。其次，分析肌肉组织代谢产物与胰岛素抵抗、炎症和淋巴细胞端粒长度的关系，后者作为衰老的指标。方法：样本包括56名健康久坐男性，预定腹股沟疝手术，年龄27至80岁。每个人都进行了人体测量，通过放射密度测定法（DEXA）进行身体成分评估，测量握力和股四头肌力量，血清生化参数（脂蛋白、肌酐、高敏C反应蛋白[hsCRP]、空腹和葡萄糖后胰岛素和葡萄糖浓度，用于通过Matsuda和HOMA-IR指数计算IR），以及提取外周白细胞用于测量端粒长度。在外科手术过程中，获得肌肉组织样品（前腹斜肌），以通过质谱法测量CER和DAG（以及根据链长和饱和度的亚种），使用电子显微镜免疫组织化学测量4-羟基-2-壬烯醛加合物（4-HNE），并通过免疫组织化学测量羧甲基-赖氨酸（CML），后者作为氧化应激（OS）的指标。结果：26例BMI> 25 k/m2，7例BMI> 30 k/m2。超重/肥胖个体在骨骼肌脂质代谢物方面没有表现出差异，但是，在具有中央脂肪分布的个体（n = 14）以及葡萄糖不耐受受试者（n = 23）中，总CER和特定长链CER亚种（20和22碳）显著增加。单核白细胞端粒长度与20和22碳CER呈负相关（rho = -0.4和-0.50 p < 0.05）。肌肉力量与任何测量的肌肉代谢物或OS标记物无关。多元回归分析接受腹部中心脂肪和端粒长度作为CER的显著预测因子（R2 = 0.28）。结论：肌肉组织中特定神经酰胺物质的积累与腹部肥胖、葡萄糖耐受不良和白细胞端粒缩短之间存在关联，但与肌肉氧化损伤或功能障碍无关。
Introduction: Background: Obesity is a risk factor for diabetes and its consequences, including accelerated ageing and mortality. The underlying factor could be accumulation of certain lipid moieties, such as ceramides (CER) and diacylgycerol (DAG) within muscle tissue, which are known to promote insulin resistance (IR), induce inflammation and oxidative injury, ultimately altering muscle function. Aim: First, to study the relationship between body composition and age (independent variables) with skeletal muscle accumulation of lipid species, oxidative injury and strength. Second, to analyze the relationship between muscle tissue metabolites and insulin resistance, inflammation and lymphocyte telomere length, the latter as an indicator of ageing. Methodology: The sample included 56 healthy sedentary males, scheduled for inguinal hernia surgery, aged 27 to 80 y. Each individual was subject to anthropometric measurements, body composition assessment through radiologic densitometry (DEXA), measurement of handgrip and quadriceps strength, serum biochemical parameters (lipoproteins, creatinine, high sensitivity C reactive protein [hsCRP], fasting and post glucose insulin and glucose concentrations for calculation of IR through the Matsuda and HOMA-IR indexes), and extraction of peripheral leukocytes for measurement of telomere length. During the surgical procedure, a sample of muscle tissue was obtained (anterior abdominal oblique) in order to measure CER and DAG (and sub species according to chain length and saturation) by mass spectrometry, 4 hydroxy-2-nonenal adducts (4-HNE) using electron microscopy immunohistochemistry, and carboxymethyl-lisine (CML) by immunohistochemistry, the latter as indicators of oxidative stress (OS). Results: Body mass index (BMI) of twenty six individuals was > 25 k/m(2), while BMI of 7 was > 30 k/m(2). Overweight/obese individuals, did not exhibit differences in skeletal muscle lipid metabolites, however total CER and specific long chain CER sub-species (20 and 22 carbon) increased significantly among individuals with a central fat distribution (n = 14) as well as in glucose intolerant subjects (n = 23). A negative association was found between mononuclear leukocyte telomere length and 20 and 22 carbon CER (rho = -0.4 and -0.5 0 p < 0.05). Muscle strength was not associated with any of the measured muscle metabolites or markers of OS. A multiple regression analysis accepted central abdominal fat and telomere length as significant predictors of CER (R2 = 0.28). Conclusions: An association was found between accumulation of specific ceramide species in muscle tissue and abdominal obesity, glucose intolerance and shortening of leukocyte telomeres, although not with muscle oxidative injury or dysfunction.