Metabolic profiling of visceral adipose tissue from obese subjects with or without metabolic syndrome
Metabolic profiling of visceral adipose tissue from obese subjects with or without metabolic syndrome
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DOI：
10.1042/bcj20170604
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发表时间：
2018-03-15
影响因子：
4.1
通讯作者：
Melino, Gerry
中科院分区：
文献类型：
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作者：
Candi, Eleonora;Tesauro, Manfredi;Melino, Gerry
肥胖是最复杂的公共卫生挑战之一，最近已达到流行病的程度。肥胖也被认为是代谢综合征患病率上升的主要原因，代谢综合征的定义是同一个体同时存在几种动脉粥样硬化的危险因素，包括血脂异常、高血压和高血糖，以及癌症。此外，五种危险因素中的三种（腹部肥胖、低高密度脂蛋白胆固醇、高甘油三酯、高空腹血糖和高血压）的存在是代谢综合征的特征，具有严重的临床后果。目前的研究是为了确定从被诊断为代谢综合征的肥胖（体重指数43-48）人类受试者、代谢健康的肥胖个体和非肥胖健康对照组中收集的内脏脂肪组织（VAT）的代谢差异。采用广泛的气相色谱/质谱（GC/MS）和液相色谱/质谱（LC/MS/MS）分析，获得了属于所有生化途径的481种代谢物的非靶向VAT代谢组学谱。我们的研究结果表明，除了与代谢综合征一致的葡萄糖水平升高的微妙标志物外，病理肥胖样本的氧化应激标志物也一致增加。在病理性肥胖受试者的组织中，除了甘油磷酸胆碱、甘油磷酸乙醇胺、甘油磷酸丝氨酸、神经酰胺和鞘脂的变化外，磷脂原水平明显升高，可能因氧化变化而升高。这些数据可能有助于认识肥胖代谢血管并发症的新途径，并可能导致创新靶向治疗的发展。
Obesity represents one of the most complex public health challenges and has recently reached epidemic proportions. Obesity is also considered to be primarily responsible for the rising prevalence of metabolic syndrome, defined as the coexistence in the same individual of several risk factors for atherosclerosis, including dyslipidemia, hypertension and hyperglycemia, as well as for cancer. Additionally, the presence of three of the five risk factors (abdominal obesity, low high-density lipoprotein cholesterol, high triglycerides, high fasting glucose and high blood pressure) characterizes metabolic syndrome, which has serious clinical consequences. The current study was conducted in order to identify metabolic differences in visceral adipose tissue (VAT) collected from obese (body mass index 43-48) human subjects who were diagnosed with metabolic syndrome, obese individuals who were metabolically healthy and nonobese healthy controls. Extensive gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS/MS) analyses were used to obtain the untargeted VAT metabolomic profiles of 481 metabolites belonging to all biochemical pathways. Our results indicated consistent increases in oxidative stress markers from the pathologically obese samples in addition to subtle markers of elevated glucose levels that may be consistent with metabolic syndrome. In the tissue derived from the pathologically obese subjects, there were significantly elevated levels of plasmalogens, which may be increased in response to oxidative changes in addition to changes in glycerolphosphorylcholine, glycerolphosphorylethanolamine glycerolphosphorylserine, ceramides and sphingolipids. These data could be potentially helpful for recognizing new pathways that underlie the metabolic-vascular complications of obesity and may lead to the development of innovative targeted therapies.