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

• Main Authors: Geraldine F. Clough, Andrew J. Chipperfield, Marjola Thanaj, Eleonora Scorletti, Philip C. Calder, Christopher D. Byrne
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2020-06-01
• Series: Frontiers in Physiology
• Subjects: microcirculation; blood flow; skin; flow-motion; non-linear complexity analysis; NAFLD
• Online Access: https://www.frontiersin.org/article/10.3389/fphys.2020.00551/full

Background/AimsIncreasing 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.MethodsMicrovascular 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.ResultsMeasurements were made in 189 adults (113 men) with NAFLD, with (n = 65) and without (n = 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 (r = −0.178, p = 0.014, and r = −0.201, p = 0.007, respectively) and enhanced liver fibrosis (ELF) score (r = −0.155, p = 0.038 and r = −0.418, p < 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 (p < 0.01 and p < 0.001) and positively with ELF score (p < 0.05 and p < 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 (p < 0.0001).ConclusionAltered microvascular network functionality occurs in adults with NAFLD suggesting a mechanistic role for dysregulated neurovascular control in individuals at risk of severe liver fibrosis.