title: Differential Patterns and Determinants of Cardiac Autonomic Nerve Dysfunction during Endotoxemia and Oral Fat Load in Humans.
abstract: The autonomic nervous system (ANS) plays an important role in regulating the metabolic homeostasis and controlling immune function. ANS alterations can be detected by reduced heart rate variability (HRV) in conditions like diabetes and sepsis. We determined the effects of experimental conditions mimicking inflammation and hyperlipidemia on HRV and heart rate (HR) in relation to the immune, metabolic, and hormonal responses resulting from these interventions. Sixteen lean healthy subjects received intravenous (i.v.) low-dose endotoxin (lipopolysaccharide [LPS]), i.v. fat, oral fat, and i.v. glycerol (control) for 6 hours, during which immune, metabolic, hormonal, and five HRV parameters (pNN50, RMSSD, low-frequency (LF) and high-frequency (HF) power, and LF/HF ratio) were monitored and energy metabolism and insulin sensitivity (M-value) were assessed. LPS infusion induced an increase (AUC) in HR and LF/HF ratio and decline in pNN50 and RMSSD, while oral fat resulted in elevated HR and a transient (hours 1-2) decrease in pNN50, RMSSD, and HF power. During LPS infusion, ΔIL-1ra levels and ΔIL-1ra and ΔIL-1ß gene expression correlated positively with ΔLF/HF ratio and inversely with ΔRMSSD. During oral fat intake, ΔGLP-1 tended to correlate positively with ΔHR and inversely with ΔpNN50 and ΔRMSSD. Following LPS infusion, lipid oxidation correlated positively with HR and inversely with pNN50 and RMSSD, whereas HRV was not related to M-value. In conclusion, suppression of vagal tone and sympathetic predominance during endotoxemia are linked to anti-inflammatory processes and lipid oxidation but not to insulin resistance, while weaker HRV changes in relation to the GLP-1 response are noted during oral fat load.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01054989.
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center at Heinrich Heine University, Leibniz Center for Diabetes Research, Düsseldorf, Germany; Department of Endocrinology and Diabetology, University Hospital, Düsseldorf, Germany; German Center for Diabetes Research (DZD), Partner Düsseldorf, Düsseldorf, Germany.
authors.forename: Dan
authors.initials: D
authors.lastname: Ziegler
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center at Heinrich Heine University, Leibniz Center for Diabetes Research, Düsseldorf, Germany; German Center for Diabetes Research (DZD), Partner Düsseldorf, Düsseldorf, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Strom
authors.affiliation: Institute of Biometrics and Epidemiology, German Diabetes Center at Heinrich Heine University, Leibniz Center for Diabetes Research, Düsseldorf, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Strassburger
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center at Heinrich Heine University, Leibniz Center for Diabetes Research, Düsseldorf, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Nowotny
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center at Heinrich Heine University, Leibniz Center for Diabetes Research, Düsseldorf, Germany; Department of Endocrinology and Diabetology, University Hospital, Düsseldorf, Germany.
authors.forename: Lejla
authors.initials: L
authors.lastname: Zahiragic
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center at Heinrich Heine University, Leibniz Center for Diabetes Research, Düsseldorf, Germany.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Nowotny
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center at Heinrich Heine University, Leibniz Center for Diabetes Research, Düsseldorf, Germany; German Center for Diabetes Research (DZD), Partner Düsseldorf, Düsseldorf, Germany.
authors.forename: Maren
authors.initials: M
authors.lastname: Carstensen-Kirberg
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center at Heinrich Heine University, Leibniz Center for Diabetes Research, Düsseldorf, Germany; German Center for Diabetes Research (DZD), Partner Düsseldorf, Düsseldorf, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Herder
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center at Heinrich Heine University, Leibniz Center for Diabetes Research, Düsseldorf, Germany; Department of Endocrinology and Diabetology, University Hospital, Düsseldorf, Germany; German Center for Diabetes Research (DZD), Partner Düsseldorf, Düsseldorf, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Szendroedi
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center at Heinrich Heine University, Leibniz Center for Diabetes Research, Düsseldorf, Germany; Department of Endocrinology and Diabetology, University Hospital, Düsseldorf, Germany; German Center for Diabetes Research (DZD), Partner Düsseldorf, Düsseldorf, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Roden
mesh_terms: D000328:Adult; D019540:Area Under Curve; D001341:Autonomic Nervous System / Q000503:physiopathology*; D002151:Calorimetry; D018592:Cross-Over Studies; D003920:Diabetes Mellitus / Q000503:physiopathology; D019446:Endotoxemia / Q000503:physiopathology*; D004731:Endotoxins / Q000737:chemistry; D005260:Female; D006321:Heart / Q000294:innervation*; D006339:Heart Rate; D006706:Homeostasis; D006801:Humans; D007249:Inflammation; D007333:Insulin Resistance; D008070:Lipopolysaccharides / Q000737:chemistry; D008297:Male; D018805:Sepsis / Q000503:physiopathology; D014630:Vagus Nerve / Q000473:pathology; D055815:Young Adult
chemical_list: D004731:Endotoxins; D008070:Lipopolysaccharides