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

doi:10.1042/CS20150777

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

Physiology

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22 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-9_α,11_α-methanoepoxy prostaglandin F_2α (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 (Thr^180/182) and extracellular signal-regulated kinase 1/2 (Erk1/2) (Ser^180/221). 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 language	English (US)
Pages (from-to)	871-880
Number of pages	10
Journal	Clinical Science
Volume	130
Issue number	11
DOIs	https://doi.org/10.1042/CS20150777
State	Published - 2016

Keywords

Basilar artery
Cerebral artery
High fat
O-GlcNAc
Vascular contraction

ASJC Scopus subject areas

Medicine(all)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1042/CS20150777

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@article{3d6cf55e1b0d4db29701d56f5433053d,

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

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 F2α (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.",

keywords = "Basilar artery, Cerebral artery, High fat, O-GlcNAc, Vascular contraction",

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

note = "Publisher Copyright: {\textcopyright} 2016 The Author(s).",

year = "2016",

doi = "10.1042/CS20150777",

language = "English (US)",

volume = "130",

pages = "871--880",

journal = "Clinical Science",

issn = "0143-5221",

publisher = "Portland Press Ltd.",

number = "11",

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TY - JOUR

T1 - High-fat diet increases O-GlcNAc levels in cerebral arteries

T2 - Link to vascular dysfunction associated with hyperlipidaemia/obesity?

AU - Lima, Victor V.

AU - Giachini, Fernanda R.

AU - Matsumoto, Takayuki

AU - Li, Weiguo

AU - Bressan, Alecsander F.M.

AU - Chawla, Dhruv

AU - Webb, R Clinton

AU - Ergul, Adviye

AU - Tostes, Rita C.

PY - 2016

Y1 - 2016

N2 - 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 F2α (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.

AB - 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 F2α (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.

KW - Basilar artery

KW - Cerebral artery

KW - High fat

KW - O-GlcNAc

KW - Vascular contraction

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U2 - 10.1042/CS20150777

DO - 10.1042/CS20150777

M3 - Article

C2 - 26929437

AN - SCOPUS:85006131049

SN - 0143-5221

VL - 130

SP - 871

EP - 880

JO - Clinical Science

JF - Clinical Science

IS - 11

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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