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Physiological disturbance in fatty liver energy metabolism converges on IGFBP2 abundance and regulation in mice and men

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Abstract
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.
Keywords
INSULIN-RESISTANCE, LIPID-METABOLISM, REDUCED EXPRESSION, SCORING, SYSTEM, ADIPOSE-TISSUE, DISEASE, OBESITY, LIPOTOXICITY, PATHOGENESIS, CHOLESTEROL, NAFLD, fatty liver metabolism, fatty liver progression, de novo, lipogenesis, IGFBP2, IGF system, methylation, SREBP-1c

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MLA
Fahlbusch, Pia, et al. “Physiological Disturbance in Fatty Liver Energy Metabolism Converges on IGFBP2 Abundance and Regulation in Mice and Men.” INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, vol. 21, no. 11, 2020, doi:10.3390/ijms21114144.
APA
Fahlbusch, P., Knebel, B., Hoerbelt, T., Barbosa, D. M., Nikolic, A., Jacob, S., … Kotzka, J. (2020). Physiological disturbance in fatty liver energy metabolism converges on IGFBP2 abundance and regulation in mice and men. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 21(11). https://doi.org/10.3390/ijms21114144
Chicago author-date
Fahlbusch, Pia, Birgit Knebel, Tina Hoerbelt, David Monteiro Barbosa, Aleksandra Nikolic, Sylvia Jacob, Hadi Al-Hasani, et al. 2020. “Physiological Disturbance in Fatty Liver Energy Metabolism Converges on IGFBP2 Abundance and Regulation in Mice and Men.” INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 21 (11). https://doi.org/10.3390/ijms21114144.
Chicago author-date (all authors)
Fahlbusch, Pia, Birgit Knebel, Tina Hoerbelt, David Monteiro Barbosa, Aleksandra Nikolic, Sylvia Jacob, Hadi Al-Hasani, Frederique Van de Velde, Yves Van Nieuwenhove, Dirk Mueller-Wieland, Bruno Lapauw, Margriet Ouwens, and Jorg Kotzka. 2020. “Physiological Disturbance in Fatty Liver Energy Metabolism Converges on IGFBP2 Abundance and Regulation in Mice and Men.” INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 21 (11). doi:10.3390/ijms21114144.
Vancouver
1.
Fahlbusch P, Knebel B, Hoerbelt T, Barbosa DM, Nikolic A, Jacob S, et al. Physiological disturbance in fatty liver energy metabolism converges on IGFBP2 abundance and regulation in mice and men. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. 2020;21(11).
IEEE
[1]
P. Fahlbusch et al., “Physiological disturbance in fatty liver energy metabolism converges on IGFBP2 abundance and regulation in mice and men,” INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, vol. 21, no. 11, 2020.
@article{8699248,
  abstract     = {{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.}},
  articleno    = {{4144}},
  author       = {{Fahlbusch, Pia and Knebel, Birgit and Hoerbelt, Tina and Barbosa, David Monteiro and Nikolic, Aleksandra and Jacob, Sylvia and Al-Hasani, Hadi and Van de Velde, Frederique and Van Nieuwenhove, Yves and Mueller-Wieland, Dirk and Lapauw, Bruno and Ouwens, Margriet and Kotzka, Jorg}},
  issn         = {{1422-0067}},
  journal      = {{INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}},
  keywords     = {{INSULIN-RESISTANCE,LIPID-METABOLISM,REDUCED EXPRESSION,SCORING,SYSTEM,ADIPOSE-TISSUE,DISEASE,OBESITY,LIPOTOXICITY,PATHOGENESIS,CHOLESTEROL,NAFLD,fatty liver metabolism,fatty liver progression,de novo,lipogenesis,IGFBP2,IGF system,methylation,SREBP-1c}},
  language     = {{eng}},
  number       = {{11}},
  pages        = {{18}},
  title        = {{Physiological disturbance in fatty liver energy metabolism converges on IGFBP2 abundance and regulation in mice and men}},
  url          = {{http://dx.doi.org/10.3390/ijms21114144}},
  volume       = {{21}},
  year         = {{2020}},
}

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