VGF peptide profiles in Type 2 diabetic patients' plasma and in obese mice

D'AMATO, FILOMENA;NOLI, BARBARA;ANGIONI, LAURA;INCANI, MICHELA;MESSANA, IRENE;MANCONI, BARBARA;SOLINAS, PAOLA;ISOLA, RAFFAELLA;MARIOTTI, STEFANO;FERRI, GIAN LUCA;COCCO, CRISTINA
2015

Abstract

To address the possible involvement of VGF peptides in obesity and diabetes, we studied type 2 diabetes (T2D) and obese patients, and high-fat diet induced obese mice. Two VGF peptides (NAPP-19 and QQET-30) were identified in human plasma by HPLC-ESI-MS. The VGF C-terminus, the above two cleaved peptides, and the TLQP-21 related peptide/s were studied using ELISA and immunohistochemistry. In euglycemic patients, plasma NAPPE and TLQP like peptides were significantly reduced with obesity (74±10 vs. 167±28, and 92±10 vs. 191±19 pmol/ml, mean+SEM, n = 10 and 6, obese vs. normal BMI, respectively, p<0.03). Upon a standard glucose load, a distinct response was shown for VGF C-terminus, TLQP and QQET-like (ERVW immunoreactive) peptides in euglycemic normal BMI patients, but was virtually abolished in euglycemic obese, and in T2D patients independently of BMI. High-fat diet induced obese mice showed reduced plasma VGF C-terminus, NAPPE and QQET-like (ERVW) peptide/s (3±0.2 vs. 4.6±0.3, 22±3.5 vs. 34±1.3, and 48±7 vs. 100±7 pmol/ml, mean+SEM, n = 8/group, obese vs. slim, respectively, p<0.03), with a loss of the response to glucose for all VGF peptides studied. In immunohistochemistry, TLQP and/or VGF C-terminus antibodies labelled VGF containing perikarya in mouse celiac ganglia, pancreatic islet cells and thin beaded nerve fibres in brown adipose tissues, with fewer in white adipose tissue. Upon the glucose load, tyrosine hydroxylase and VGF C-terminus immunoreactive axons became apparent in pancreatic islets of slim animals, but not in obese animals. Alltogether, a significant loss of VGF peptide immunoreactivity and/or their response to glucose was demonstrated in obese patients, with or without T2D, in parallel with a similar loss in high-fat diet induced obese mice. An involvement of VGF in metabolic regulations, including those of brown and/or white adipose tissues is underlined, and may point out specific VGF peptides as potential targets for diagnosis and/or treatment.
2015
Inglese
10
11
e0142333
16
http://www.plosone.org/article/fetchObject.action?uri=info:doi/10.1371/journal.pone.0142333&representation=PDF
Esperti anonimi
internazionale
scientifica
Adult; Aged; Aged, 80 and over; Amino Acid Sequence; Animals; Chromatography, High Pressure Liquid; Diabetes Mellitus, Type 2; Diet, High-Fat; Enzyme-Linked Immunosorbent Assay; Humans; Immunohistochemistry; Male; Mice; Microscopy, Fluorescence; Middle Aged; Molecular Sequence Data; Neuropeptides; Obesity; Peptide Fragments; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry; Agricultural and Biological Sciences (all); Biochemistry, Genetics and Molecular Biology (all); Medicine (all)
Article number e0142333
no
D'Amato, Filomena; Noli, Barbara; Angioni, Laura; Cossu, E; Incani, Michela; Messana, Irene; Manconi, Barbara; Solinas, Paola; Isola, Raffaella; Mariotti, Stefano; Ferri, GIAN LUCA; Cocco, Cristina
1.1 Articolo in rivista
info:eu-repo/semantics/article
1 Contributo su Rivista::1.1 Articolo in rivista
262
12
open
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