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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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.
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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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