title: Markers of sympathetic nervous system activity associate with complex plasma lipids in metabolic syndrome subjects.
abstract: 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, GM3ganglioside, sphingomyelin, phosphatidylcholine, alkyl- and alkenylphosphatidylcholine, phosphatidylinositol and free cholesterol; HR marginally (p = or <0.1>0.05) with ceramide, GM3ganglioside, 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.
authors.affiliation: Baker IDI Heart & Diabetes Institute, Melbourne, Australia. Electronic address: paul.nestel@bakeridi.edu.au.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Nestel
authors.affiliation: 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.
authors.forename: Anmar A
authors.initials: AA
authors.lastname: Khan
authors.affiliation: Baker IDI Heart & Diabetes Institute, Melbourne, Australia.
authors.forename: Nora E
authors.initials: NE
authors.lastname: Straznicky
authors.affiliation: Baker IDI Heart & Diabetes Institute, Melbourne, Australia.
authors.forename: Natalie A
authors.initials: NA
authors.lastname: Mellett
authors.affiliation: Baker IDI Heart & Diabetes Institute, Melbourne, Australia.
authors.forename: Kaushala
authors.initials: K
authors.lastname: Jayawardana
authors.affiliation: Baker IDI Heart & Diabetes Institute, Melbourne, Australia.
authors.forename: Piyushkumar A
authors.initials: PA
authors.lastname: Mundra
authors.affiliation: Baker IDI Heart & Diabetes Institute, Melbourne, Australia.
authors.forename: Gavin W
authors.initials: GW
authors.lastname: Lambert
authors.affiliation: Baker IDI Heart & Diabetes Institute, Melbourne, Australia; Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Meikle
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002518:Ceramides / Q000097:blood; D003430:Cross-Sectional Studies; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood*; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood* / Q000175:diagnosis / Q000503:physiopathology; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D009765:Obesity / Q000097:blood* / Q000175:diagnosis / Q000503:physiopathology; D010743:Phospholipids / Q000097:blood; D013107:Sphingolipids / Q000097:blood; D013564:Sympathetic Nervous System / Q000378:metabolism* / Q000503:physiopathology; D009435:Synaptic Transmission; D053719:Tandem Mass Spectrometry
chemical_list: D015415:Biomarkers; D002518:Ceramides; D005230:Fatty Acids, Nonesterified; D008055:Lipids; D010743:Phospholipids; D013107:Sphingolipids; D009638:Norepinephrine
keywords: Insulin resistance; Lipidomics; Metabolic syndrome; NEFA; Norepinephrine; Sympathetic nervous system activity