Physiological Disturbance in Fatty Liver Energy Metabolism Converges on IGFBP2 Abundance and Regulation in Mice and Men.

International Journal of Molecular Sciences
Pia FahlbuschJorg Kotzka

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...Continue Reading

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Citations

Oct 31, 2020·The Journal of Clinical Endocrinology and Metabolism·Takara L StanleySteven K Grinspoon
Nov 8, 2020·Molecular Metabolism·Wenke Jonas, Annette Schürmann

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Datasets Mentioned

BETA
GSE139901

Methods Mentioned

BETA
transgenic
biopsies
gastric bypass
biopsy
PCR
Assay
ELISA

Clinical Trials Mentioned

NCT00740194

Software Mentioned

Transcriptome Analysis ConsoleTM
GraphPad Prism
SPSS Statistics

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