Clinical Nutrition Research

The Korean Society of Clinical Nutrition (한국임상영양학회)
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Lipocalin-2 Secreted by the Liver Regulates Neuronal Cell Function Through AKT-Dependent Signaling in Hepatic Encephalopathy Mouse Model

  • Danbi Jo (Department of Anatomy, Chonnam National University Medical School) ;
  • Yoon Seok Jung (Department of Anatomy, Chonnam National University Medical School) ;
  • Juhyun Song (Department of Anatomy, Chonnam National University Medical School)
  • Received : 2023.01.08
  • Accepted : 2023.03.23
  • Published : 2023.04.30
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Abstract

Hepatic encephalopathy (HE) associated with liver failure is accompanied by hyperammonemia, severe inflammation, depression, anxiety, and memory deficits as well as liver injury. Recent studies have focused on the liver-brain-inflammation axis to identify a therapeutic solution for patients with HE. Lipocalin-2 is an inflammation-related glycoprotein that is secreted by various organs and is involved in cellular mechanisms including iron homeostasis, glucose metabolism, cell death, neurite outgrowth, and neurogenesis. In this study, we investigated that the roles of lipocalin-2 both in the brain cortex of mice with HE and in Neuro-2a (N2A) cells. We detected elevated levels of lipocalin-2 both in the plasma and liver in a bile duct ligation mouse model of HE. We confirmed changes in cytokine expression, such as interleukin-1β, cyclooxygenase 2 expression, and iron metabolism related to gene expression through AKT-mediated signaling both in the brain cortex of mice with HE and N2A cells. Our data showed negative effects of hepatic lipocalin-2 on cell survival, iron homeostasis, and neurite outgrowth in N2A cells. Thus, we suggest that regulation of lipocalin-2 in the brain in HE may be a critical therapeutic approach to alleviate neuropathological problems focused on the liver-brain axis.

Keywords

Acknowledgement

This study was supported by grant NRF-2022R1A2C1006125 (Juhyun Song) from the National Research Foundation of Korea (NRF), Republic of Korea, and HCRI 22019 from the Chonnam National University Hwasun Hospital Institute for Biomedical Science, Korea (Juhyun Song). The authors acknowledged Biorender.com in creating the figures.

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