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Physiological Disturbance in Fatty Liver Energy Metabolism Converges on IGFBP2 Abundance and Regulation in Mice and Men
Fatty liver occurs from simple steatosis with accumulated hepatic lipids and hepatic insulin resistance to severe steatohepatitis, with aggravated lipid accumulation and systemic insulin resistance, but this progression is still poorly understood. Analyses of hepatic gene expression patterns from al...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312731/ https://www.ncbi.nlm.nih.gov/pubmed/32532003 http://dx.doi.org/10.3390/ijms21114144 |
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author | Fahlbusch, Pia Knebel, Birgit Hörbelt, Tina Barbosa, David Monteiro Nikolic, Aleksandra Jacob, Sylvia Al-Hasani, Hadi Van de Velde, Frederique Van Nieuwenhove, Yves Müller-Wieland, Dirk Lapauw, Bruno Ouwens, D. Margriet Kotzka, Jorg |
author_facet | Fahlbusch, Pia Knebel, Birgit Hörbelt, Tina Barbosa, David Monteiro Nikolic, Aleksandra Jacob, Sylvia Al-Hasani, Hadi Van de Velde, Frederique Van Nieuwenhove, Yves Müller-Wieland, Dirk Lapauw, Bruno Ouwens, D. Margriet Kotzka, Jorg |
author_sort | Fahlbusch, Pia |
collection | PubMed |
description | Fatty liver occurs from simple steatosis with accumulated hepatic lipids and hepatic insulin resistance to severe steatohepatitis, with aggravated lipid accumulation and systemic insulin resistance, but this progression is still poorly understood. Analyses of hepatic gene expression patterns from alb-SREBP-1c mice with moderate, or aP2-SREBP-1c mice with aggravated, hepatic lipid accumulation revealed IGFBP2 as key nodal molecule differing between moderate and aggravated fatty liver. Reduced IGFBP2 expression in aggravated fatty liver was paralleled with promoter hypermethylation, reduced hepatic IGFBP2 secretion and IGFBP2 circulating in plasma. Physiologically, the decrease of IGFBP2 was accompanied with reduced fatty acid oxidation and increased de novo lipogenesis potentially mediated by IGF1 in primary hepatocytes. Furthermore, methyltransferase and sirtuin activities were enhanced. In humans, IGFBP2 serum concentration was lower in obese men with non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) compared to non-obese controls, and liver fat reduction by weight-loss intervention correlated with an increase of IGFBP2 serum levels. In conclusion, hepatic IGFBP2 abundance correlates to its circulating level and is related to hepatic energy metabolism and de novo lipogenesis. This designates IGFBP2 as non-invasive biomarker for fatty liver disease progression and might further provide an additional variable for risk prediction for pathogenesis of fatty liver in diabetes subtype clusters. |
format | Online Article Text |
id | pubmed-7312731 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-73127312020-06-26 Physiological Disturbance in Fatty Liver Energy Metabolism Converges on IGFBP2 Abundance and Regulation in Mice and Men Fahlbusch, Pia Knebel, Birgit Hörbelt, Tina Barbosa, David Monteiro Nikolic, Aleksandra Jacob, Sylvia Al-Hasani, Hadi Van de Velde, Frederique Van Nieuwenhove, Yves Müller-Wieland, Dirk Lapauw, Bruno Ouwens, D. Margriet Kotzka, Jorg Int J Mol Sci Article Fatty liver occurs from simple steatosis with accumulated hepatic lipids and hepatic insulin resistance to severe steatohepatitis, with aggravated lipid accumulation and systemic insulin resistance, but this progression is still poorly understood. Analyses of hepatic gene expression patterns from alb-SREBP-1c mice with moderate, or aP2-SREBP-1c mice with aggravated, hepatic lipid accumulation revealed IGFBP2 as key nodal molecule differing between moderate and aggravated fatty liver. Reduced IGFBP2 expression in aggravated fatty liver was paralleled with promoter hypermethylation, reduced hepatic IGFBP2 secretion and IGFBP2 circulating in plasma. Physiologically, the decrease of IGFBP2 was accompanied with reduced fatty acid oxidation and increased de novo lipogenesis potentially mediated by IGF1 in primary hepatocytes. Furthermore, methyltransferase and sirtuin activities were enhanced. In humans, IGFBP2 serum concentration was lower in obese men with non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) compared to non-obese controls, and liver fat reduction by weight-loss intervention correlated with an increase of IGFBP2 serum levels. In conclusion, hepatic IGFBP2 abundance correlates to its circulating level and is related to hepatic energy metabolism and de novo lipogenesis. This designates IGFBP2 as non-invasive biomarker for fatty liver disease progression and might further provide an additional variable for risk prediction for pathogenesis of fatty liver in diabetes subtype clusters. MDPI 2020-06-10 /pmc/articles/PMC7312731/ /pubmed/32532003 http://dx.doi.org/10.3390/ijms21114144 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Fahlbusch, Pia Knebel, Birgit Hörbelt, Tina Barbosa, David Monteiro Nikolic, Aleksandra Jacob, Sylvia Al-Hasani, Hadi Van de Velde, Frederique Van Nieuwenhove, Yves Müller-Wieland, Dirk Lapauw, Bruno Ouwens, D. Margriet Kotzka, Jorg Physiological Disturbance in Fatty Liver Energy Metabolism Converges on IGFBP2 Abundance and Regulation in Mice and Men |
title | Physiological Disturbance in Fatty Liver Energy Metabolism Converges on IGFBP2 Abundance and Regulation in Mice and Men |
title_full | Physiological Disturbance in Fatty Liver Energy Metabolism Converges on IGFBP2 Abundance and Regulation in Mice and Men |
title_fullStr | Physiological Disturbance in Fatty Liver Energy Metabolism Converges on IGFBP2 Abundance and Regulation in Mice and Men |
title_full_unstemmed | Physiological Disturbance in Fatty Liver Energy Metabolism Converges on IGFBP2 Abundance and Regulation in Mice and Men |
title_short | Physiological Disturbance in Fatty Liver Energy Metabolism Converges on IGFBP2 Abundance and Regulation in Mice and Men |
title_sort | physiological disturbance in fatty liver energy metabolism converges on igfbp2 abundance and regulation in mice and men |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312731/ https://www.ncbi.nlm.nih.gov/pubmed/32532003 http://dx.doi.org/10.3390/ijms21114144 |
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