High-fat diet alters N-glycosylation of PTPRJ in murine liver.

Autor: Ulke J; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Diagnostic Laboratory Medicine, Clinical Chemistry and Pathobiochemistry, Augustenburger Platz 1, 13353 Berlin, Germany; Charité - Universitätsmedizin Berlin, Max Rubner Center (MRC) for Cardiovascular Metabolic Renal Research, Berlin, Germany., Schwedler C; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Diagnostic Laboratory Medicine, Clinical Chemistry and Pathobiochemistry, Augustenburger Platz 1, 13353 Berlin, Germany., Krüger J; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Diagnostic Laboratory Medicine, Clinical Chemistry and Pathobiochemistry, Augustenburger Platz 1, 13353 Berlin, Germany; Charité - Universitätsmedizin Berlin, Max Rubner Center (MRC) for Cardiovascular Metabolic Renal Research, Berlin, Germany., Stein V; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Diagnostic Laboratory Medicine, Clinical Chemistry and Pathobiochemistry, Augustenburger Platz 1, 13353 Berlin, Germany; Charité - Universitätsmedizin Berlin, Max Rubner Center (MRC) for Cardiovascular Metabolic Renal Research, Berlin, Germany., Geserick P; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Diagnostic Laboratory Medicine, Clinical Chemistry and Pathobiochemistry, Augustenburger Platz 1, 13353 Berlin, Germany; Charité - Universitätsmedizin Berlin, Max Rubner Center (MRC) for Cardiovascular Metabolic Renal Research, Berlin, Germany., Kleinridders A; Department of Molecular and Experimental Nutritional Medicine, Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany., Kappert K; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Diagnostic Laboratory Medicine, Clinical Chemistry and Pathobiochemistry, Augustenburger Platz 1, 13353 Berlin, Germany; Charité - Universitätsmedizin Berlin, Max Rubner Center (MRC) for Cardiovascular Metabolic Renal Research, Berlin, Germany. Electronic address: kai.kappert@charite.de.
Jazyk: angličtina
Zdroj: The Journal of nutritional biochemistry [J Nutr Biochem] 2024 Jan; Vol. 123, pp. 109500. Date of Electronic Publication: 2023 Oct 22.
DOI: 10.1016/j.jnutbio.2023.109500
Abstrakt: Protein tyrosine phosphatases (PTPs) regulate multiple signaling pathways. Disruption of tyrosine phosphorylation through imbalanced action between protein tyrosine kinases (RTKs) and PTPs is a hallmark of metabolic disorders, including insulin resistance. A representative member of the receptor-type PTP family, PTPRJ (DEP-1), was previously identified as a negative regulator of insulin signaling and possesses post-translational glycosylation sites. In this regard, it seems of great importance to decipher the structure of PTPRJ's glycosylation, particularly in the context of metabolic disturbances, but this has not been done in detail. Thus, here we aimed at characterizing the glycosylation pattern of PTPRJ in liver. We show that N-glycosylation accounts for up to half of PTPRJ's molecular weight. Applying mass spectrometry, we detected increased levels of high-mannose structures in PTPRJ in liver tissue of obese mice compared to lean littermates. In addition, complex neutral structures without fucose were also elevated in PTPRJ of high-fat diet (HFD) mice. Conversely, complex fucosylated N-glycans as well as sialylated bi- and triantennary N-glycans, were significantly reduced in PTPRJ of HFD-derived liver tissue compared to LFD by ∼two fold (P≤.01, P≤.0001 and P≤.001, respectively). In congruence with these findings, the mannosidase MAN2A1, responsible for the conversion of high-mannose to complex N-glycans, was significantly downregulated under HFD conditions. Here we present for the first time that HFD-induced obesity impacts on the glycosylation pattern of the insulin signaling component PTPRJ in liver. These findings may inspire new research on the glycosylation of PTPs in metabolic diseases and may open up new therapeutic approaches.
Competing Interests: Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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