Abstract

Despite the ever-increasing prevalence of non-alcoholic fatty liver disease (NAFLD), the etiology and pathogenesis remain poorly understood. This is due, in part, to the liver’s complex physiology and architecture. The liver maintains glucose and lipid homeostasis by coordinating numerous metabolic processes with great efficiency. This is made possible by the spatial compartmentalization of metabolic pathways a phenomenon known as liver zonation. Despite the importance of zonation to normal liver function, it is unresolved if and how perturbations to liver zonation can drive hepatic pathophysiology and NAFLD development. While hepatocyte heterogeneity has been identified over a century ago, its examination had been severely hindered due to technological limitations. Recent advances in single cell analysis and imaging technologies now permit further characterization of cells across the liver lobule. This review summarizes the advances in examining liver zonation and elucidating its regulatory role in liver physiology and pathology. Understanding the spatial organization of metabolism is vital to further our knowledge of liver disease and to provide targeted therapeutic avenues.

Highlights

  • One of the central roles of the liver is maintaining energy homeostasis by preserving blood glucose levels

  • Using laser capture microdissection (LCM) to separate zones and pathway analysis with RNA sequencing data, McEnerney et al (2017) demonstrated in human liver lobules that immune response pathways were localized to periportal regions while xenobiotic metabolism is predominantly in pericentral cells

  • Single cell and bulk RNA sequencing has allowed a vast array of genes involved in liver zonation to be examined, which is pertinent for human tissues where the amount of sample obtained can often be a limiting factor in the type analyses ran

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Summary

Introduction

One of the central roles of the liver is maintaining energy homeostasis by preserving blood glucose levels. Using bulk RNA-seq, human hepatocyte gene expression profiles have been created showing that periportal and pericentral zones are regulated in part, by gut derived toxins and xenobiotic metabolisms, respectively (McEnerney et al, 2017). Using LCM to separate zones and pathway analysis with RNA sequencing data, McEnerney et al (2017) demonstrated in human liver lobules that immune response pathways were localized to periportal regions while xenobiotic metabolism is predominantly in pericentral cells.

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