High-fat diet increases O-GlcNAc levels in cerebral arteries: Link to vascular dysfunction associated with hyperlipidaemia/obesity?

Victor V. Lima, Fernanda R. Giachini, Takayuki Matsumoto, Weiguo Li, Alecsander F.M. Bressan, Dhruv Chawla, R Clinton Webb, Adviye Ergul, Rita C. Tostes

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Obesity and high fat intake induce alterations in vascular function and structure. Aberrant O-GlcNAcylation (O-GlcNAc) of vascular proteins has been implicated in vascular dysfunction associated with cardiovascular and metabolic diseases. In the present study, we tested the hypothesis that high-fat diet (HFD)-mediated increases in O-GlcNAc-modified proteins contribute to cerebrovascular dysfunction. O-GlcNAc-protein content was increased in arteries from male Wistar rats treated with a HFD (45% fat) for 12 weeks compared with arteries from rats on control diet (CD). HFD augmented body weight [(g) 550± 10 compared with 502± 10 CD], increased plasma triacylglycerols [(mg/dl) 160± 20 compared with 95± 15 CD] and increased contractile responses of basilar arteries to serotonin [5-hydroxytryptamine (5-HT)] [(pD2) 7.0± 0.1 compared with 6.7±0.09 CD] and the thromboxane analogue 9,11-dideoxy-9α,11α-methanoepoxy prostaglandin F (U-46619) [(pD2) 7.2± 0.1 compared with 6.8± 0.09 CD]. Of importance, increased levels of O-GlcNAc [induced by 24 h-incubation of vessels with a potent inhibitor of O-GlcNAcase (OGA), O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino-N-phenylcarbamate (PugNAc)] increased basilar artery contractions in response to U-46619 [(pD2) 7.4± 0.07 compared with 6.8± 0.08 CD] and 5-HT [(pD2) 7.5± 0.06 compared with 7.1± 0.1 CD]. Vessels from rats on the HFD for 12 weeks and vessels treated with PugNAc displayed increased phosphorylation of p38 (Thr180/182) and extracellular signal-regulated kinase 1/2 (Erk1/2) (Ser180/221). Increased 5HT-induced contractions in arteries from rats on the HFD or in arteries incubated with PugNAc were abrogated by mitogen-activated protein kinase (MAPK) inhibitors. Our data show that HFD augments cerebrovascular O-GlcNAc and this modification contributes to increased contractile responses and to the activation of the MAPK pathway in the rat basilar artery.

Original languageEnglish (US)
Pages (from-to)871-880
Number of pages10
JournalClinical Science
Volume130
Issue number11
DOIs
StatePublished - 2016

Keywords

  • Basilar artery
  • Cerebral artery
  • High fat
  • O-GlcNAc
  • Vascular contraction

ASJC Scopus subject areas

  • Medicine(all)

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    Lima, V. V., Giachini, F. R., Matsumoto, T., Li, W., Bressan, A. F. M., Chawla, D., Webb, R. C., Ergul, A., & Tostes, R. C. (2016). High-fat diet increases O-GlcNAc levels in cerebral arteries: Link to vascular dysfunction associated with hyperlipidaemia/obesity? Clinical Science, 130(11), 871-880. https://doi.org/10.1042/CS20150777