AUTHOR=Clough Geraldine F. , Chipperfield Andrew J. , Thanaj Marjola , Scorletti Eleonora , Calder Philip C. , Byrne Christopher D. 

TITLE=Dysregulated Neurovascular Control Underlies Declining Microvascular Functionality in People With Non-alcoholic Fatty Liver Disease (NAFLD) at Risk of Liver Fibrosis

JOURNAL=Frontiers in Physiology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2020.00551

DOI=10.3389/fphys.2020.00551

ISSN=1664-042X

ABSTRACT=<sec><title>Background/Aims</title><p>Increasing evidence shows that non-alcoholic fatty liver disease (NAFLD) is associated with dysregulation of microvascular perfusion independently of established cardio-metabolic risk factors. We investigated whether hepatic manifestations of NAFLD such as liver fibrosis and liver fat are associated with microvascular hemodynamics through dysregulation of neurovascular control.</p></sec><sec><title>Methods</title><p>Microvascular dilator (post-occlusive reactive hyperemia) and sympathetically mediated constrictor (deep inspiratory breath-hold) responses were measured at the forearm and finger, respectively, using laser Doppler fluximetry. Non-linear complexity-based analysis was used to assess the information content and variability of the resting blood flux (BF) signals, attributable to oscillatory flow-motion activity, and over multiple sampling frequencies.</p></sec><sec><title>Results</title><p>Measurements were made in 189 adults (113 men) with NAFLD, with (<italic>n</italic> = 65) and without (<italic>n</italic> = 124) type 2 diabetes mellitus (T2DM), age = 50.9 ± 11.7 years (mean ± SD). Microvascular dilator and constrictor capacity were both negatively associated with age (<italic>r</italic> = −0.178, <italic>p</italic> = 0.014, and <italic>r</italic> = −0.201, <italic>p</italic> = 0.007, respectively) and enhanced liver fibrosis (ELF) score (<italic>r</italic> = −0.155, <italic>p</italic> = 0.038 and <italic>r</italic> = −0.418, <italic>p</italic> &lt; 0.0001, respectively). There was no association with measures of liver fat, obesity or T2DM. Lempel-Ziv complexity (LZC) and sample entropy (SE) of the BF signal measured at the two skin sites were associated negatively with age (<italic>p</italic> &lt; 0.01 and <italic>p</italic> &lt; 0.001) and positively with ELF score (<italic>p</italic> &lt; 0.05 and <italic>p</italic> &lt; 0.0001). In individuals with an ELF score ≥7.8 the influence of both neurogenic and respiratory flow-motion activity on LZC was up-rated (<italic>p</italic> &lt; 0.0001).</p></sec><sec><title>Conclusion</title><p>Altered microvascular network functionality occurs in adults with NAFLD suggesting a mechanistic role for dysregulated neurovascular control in individuals at risk of severe liver fibrosis.</p></sec>