Nestel Paul J, Khan Anmar A, Straznicky Nora E, Mellett Natalie A, Jayawardana Kaushala, Mundra Piyushkumar A, Lambert Gavin W, Meikle Peter J
Baker IDI Heart & Diabetes Institute, Melbourne, Australia.
Baker IDI Heart & Diabetes Institute, Melbourne, Australia; Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia; Faculty of Medical Sciences, Unm Al-Qura University, Makkah, Saudi Arabia.
Atherosclerosis. 2017 Jan;256:21-28. doi: 10.1016/j.atherosclerosis.2016.11.032. Epub 2016 Dec 1.
Plasma sphingolipids including ceramides, and gangliosides are associated with insulin resistance (IR) through effects on insulin signalling and glucose metabolism. Our studies of subjects with metabolic syndrome (MetS) showed close relationships between IR and sympathetic nervous system (SNS) activity including arterial norepinephrine (NE). We have therefore investigated possible associations of IR and SNS activity with complex lipids that are involved in both insulin sensitivity and neurotransmission.
We performed a cross-sectional assessment of 23 lipid classes/subclasses (total 339 lipid species) by tandem mass spectrometry in 94 overweight untreated subjects with IR (quantified by HOMA-IR, Matsuda index and plasma insulin).
Independently of IR parameters, several circulating complex lipids associated significantly with arterial NE and NEFA (non-esterified fatty acids) and marginally with heart rate (HR). After accounting for BMI, HOMA-IR, systolic BP, age, gender, and correction for multiple comparisons, these associations were significant (p < 0.05): NE with ceramide, phosphatidylcholine, alkyl- and alkenylphosphatidylcholine and free cholesterol; NEFA with mono- di- and trihexosylceramide, G ganglioside, sphingomyelin, phosphatidylcholine, alkyl- and alkenylphosphatidylcholine, phosphatidylinositol and free cholesterol; HR marginally (p = or <0.1>0.05) with ceramide, G ganglioside, sphingomyelin, lysophosphatidylcholine, phosphatidylinositol, lysophosphatidylinositol and free cholesterol. Multiple subspecies of these lipids significantly associated with NE and NEFA. None of the IR biomarkers associated significantly with lipid classes/subclasses after correction for multiple comparisons.
This is the first demonstration that arterial norepinephrine and NEFA, that reflect both SNS activity and IR, associate significantly with circulating complex lipids independently of IR, suggesting a role for such lipids in neural mechanisms operating in MetS.
包括神经酰胺和神经节苷脂在内的血浆鞘脂类物质通过对胰岛素信号传导和葡萄糖代谢的影响与胰岛素抵抗（IR）相关。我们对代谢综合征（MetS）患者的研究表明，IR与交感神经系统（SNS）活性（包括动脉去甲肾上腺素（NE））之间存在密切关系。因此，我们研究了IR和SNS活性与参与胰岛素敏感性和神经传递的复合脂质之间可能存在的关联。
我们采用串联质谱法对94名未经治疗的超重IR患者（通过HOMA-IR、松田指数和血浆胰岛素进行量化）的23种脂质类别/亚类（共339种脂质种类）进行了横断面评估。
独立于IR参数，几种循环复合脂质与动脉NE和NEFA（非酯化脂肪酸）显著相关，与心率（HR）有微弱关联。在考虑BMI、HOMA-IR、收缩压、年龄、性别并对多重比较进行校正后，这些关联具有显著性（p < 0.05）：NE与神经酰胺、磷脂酰胆碱、烷基和烯基磷脂酰胆碱以及游离胆固醇相关；NEFA与单、二和三己糖神经酰胺、G神经节苷脂、鞘磷脂、磷脂酰胆碱、烷基和烯基磷脂酰胆碱、磷脂酰肌醇以及游离胆固醇相关；HR与神经酰胺、G神经节苷脂、鞘磷脂、溶血磷脂酰胆碱、磷脂酰肌醇、溶血磷脂酰肌醇以及游离胆固醇有微弱关联（p = 或<0.1>0.05）。这些脂质的多个亚类与NE和NEFA显著相关。在校正多重比较后，没有一种IR生物标志物与脂质类别/亚类显著相关。
这是首次证明反映SNS活性和IR的动脉去甲肾上腺素和NEFA与循环复合脂质显著相关，且独立于IR，表明此类脂质在MetS的神经机制中发挥作用。
