The Putative Antilipogenic Role of NRG4 and ERBB4: First Expression Study on Human Liver Samples

Background: Epidermal growth factor receptor 4 (ERBB4) and neuregulin 4 (NRG4) have been shown to reduce steatosis and prevent the development of non-alcoholic steatohepatitis in mouse models, but little to nothing is known about their role in non-alcoholic fatty liver disease (NA...

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Main Authors: Maria Bograya, Maria Vulf, Anastasia Minchenko, Natalia Gazatova, Georgy Kuznetsov, Natalia Todosenko, Larisa Volkova, Pavel Ivanov, Larisa Litvinova
Format: Article
Language:English
Published: IMR Press 2024-12-01
Series:Frontiers in Bioscience-Landmark
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Online Access:https://www.imrpress.com/journal/FBL/29/12/10.31083/j.fbl2912414
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author Maria Bograya
Maria Vulf
Anastasia Minchenko
Natalia Gazatova
Georgy Kuznetsov
Natalia Todosenko
Larisa Volkova
Pavel Ivanov
Larisa Litvinova
author_facet Maria Bograya
Maria Vulf
Anastasia Minchenko
Natalia Gazatova
Georgy Kuznetsov
Natalia Todosenko
Larisa Volkova
Pavel Ivanov
Larisa Litvinova
author_sort Maria Bograya
collection DOAJ
description Background: Epidermal growth factor receptor 4 (ERBB4) and neuregulin 4 (NRG4) have been shown to reduce steatosis and prevent the development of non-alcoholic steatohepatitis in mouse models, but little to nothing is known about their role in non-alcoholic fatty liver disease (NAFLD) in humans. This study is the first to investigate the expression of ERBB4 and NRG4 mRNAs and their role in lipid metabolism in the livers of individuals with obesity, type 2 diabetes and biopsy-proven NAFLD. Methods: Liver biospecimens were obtained intraoperatively from 80 individuals. Quantitative reverse transcription polymerase chain reaction was used to measure the expression levels of mRNAs ERBB4 and NRG4, as well as key lipogenesis genes in the liver tissue of the donors. Histological analysis was conducted on liver biopsies from 36 subjects, and the levels of the examined transcripts were compared with the stage of NAFLD. Results: In individuals with elevated body mass index (BMI), ERBB4 and NRG4 levels decreased, while ACACA levels increased. A strong negative correlation was observed between NRG4 and ACACA levels. No deregulation of the analyzed transcripts was detected in NAFLD. Conclusions: The study demonstrates a decrease in ERBB4 and NRG4 mRNA expression in the livers of subjects with high BMI but not in those with NAFLD. The correlation of the studied transcripts with major lipogenesis genes was assessed, and on this basis a putative scheme for NRG4-mediated suppression of hepatic de novo lipogenesis was hypothesised, offering new research vectors in this field.
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spelling doaj-art-843c910104e646e29356d4508d6ea3de2024-12-30T11:39:30ZengIMR PressFrontiers in Bioscience-Landmark2768-67012024-12-01291241410.31083/j.fbl2912414S2768-6701(24)01547-8The Putative Antilipogenic Role of NRG4 and ERBB4: First Expression Study on Human Liver SamplesMaria Bograya0Maria Vulf1Anastasia Minchenko2Natalia Gazatova3Georgy Kuznetsov4Natalia Todosenko5Larisa Volkova6Pavel Ivanov7Larisa Litvinova8Center for Immunology and Cellular Biotechnology, Institute of Medicine and Life Sciences, Immanuel Kant Baltic Federal University, 236001 Kaliningrad, RussiaCenter for Immunology and Cellular Biotechnology, Institute of Medicine and Life Sciences, Immanuel Kant Baltic Federal University, 236001 Kaliningrad, RussiaCenter for Immunology and Cellular Biotechnology, Institute of Medicine and Life Sciences, Immanuel Kant Baltic Federal University, 236001 Kaliningrad, RussiaCenter for Immunology and Cellular Biotechnology, Institute of Medicine and Life Sciences, Immanuel Kant Baltic Federal University, 236001 Kaliningrad, RussiaSurgical Department, Regional Clinical Hospital Kaliningrad, 236035 Kaliningrad, RussiaCenter for Immunology and Cellular Biotechnology, Institute of Medicine and Life Sciences, Immanuel Kant Baltic Federal University, 236001 Kaliningrad, RussiaMedical Faculty, Moscow University for Industry and Finance “Synergy”, 125190 Moscow, RussiaCenter for Immunology and Cellular Biotechnology, Institute of Medicine and Life Sciences, Immanuel Kant Baltic Federal University, 236001 Kaliningrad, RussiaCenter for Immunology and Cellular Biotechnology, Institute of Medicine and Life Sciences, Immanuel Kant Baltic Federal University, 236001 Kaliningrad, RussiaBackground: Epidermal growth factor receptor 4 (ERBB4) and neuregulin 4 (NRG4) have been shown to reduce steatosis and prevent the development of non-alcoholic steatohepatitis in mouse models, but little to nothing is known about their role in non-alcoholic fatty liver disease (NAFLD) in humans. This study is the first to investigate the expression of ERBB4 and NRG4 mRNAs and their role in lipid metabolism in the livers of individuals with obesity, type 2 diabetes and biopsy-proven NAFLD. Methods: Liver biospecimens were obtained intraoperatively from 80 individuals. Quantitative reverse transcription polymerase chain reaction was used to measure the expression levels of mRNAs ERBB4 and NRG4, as well as key lipogenesis genes in the liver tissue of the donors. Histological analysis was conducted on liver biopsies from 36 subjects, and the levels of the examined transcripts were compared with the stage of NAFLD. Results: In individuals with elevated body mass index (BMI), ERBB4 and NRG4 levels decreased, while ACACA levels increased. A strong negative correlation was observed between NRG4 and ACACA levels. No deregulation of the analyzed transcripts was detected in NAFLD. Conclusions: The study demonstrates a decrease in ERBB4 and NRG4 mRNA expression in the livers of subjects with high BMI but not in those with NAFLD. The correlation of the studied transcripts with major lipogenesis genes was assessed, and on this basis a putative scheme for NRG4-mediated suppression of hepatic de novo lipogenesis was hypothesised, offering new research vectors in this field.https://www.imrpress.com/journal/FBL/29/12/10.31083/j.fbl2912414erbb4nrg4obesitynafldsteatosisnash
spellingShingle Maria Bograya
Maria Vulf
Anastasia Minchenko
Natalia Gazatova
Georgy Kuznetsov
Natalia Todosenko
Larisa Volkova
Pavel Ivanov
Larisa Litvinova
The Putative Antilipogenic Role of NRG4 and ERBB4: First Expression Study on Human Liver Samples
Frontiers in Bioscience-Landmark
erbb4
nrg4
obesity
nafld
steatosis
nash
title The Putative Antilipogenic Role of NRG4 and ERBB4: First Expression Study on Human Liver Samples
title_full The Putative Antilipogenic Role of NRG4 and ERBB4: First Expression Study on Human Liver Samples
title_fullStr The Putative Antilipogenic Role of NRG4 and ERBB4: First Expression Study on Human Liver Samples
title_full_unstemmed The Putative Antilipogenic Role of NRG4 and ERBB4: First Expression Study on Human Liver Samples
title_short The Putative Antilipogenic Role of NRG4 and ERBB4: First Expression Study on Human Liver Samples
title_sort putative antilipogenic role of nrg4 and erbb4 first expression study on human liver samples
topic erbb4
nrg4
obesity
nafld
steatosis
nash
url https://www.imrpress.com/journal/FBL/29/12/10.31083/j.fbl2912414
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