Tarek A. M. Almabrouk, Anna D. White, Azizah B. Ugusman, Dominik S. Skiba, Omar J. Katwan, Husam Alganga, Tomasz J. Guzik, Rhian M. Touyz, Ian P. Salt, Simon Kennedy
Abstract
Background and aim:
Perivascular adipose tissue (PVAT) positively regulates vascular function through production of factors such as adiponectin but this effect is attenuated in obesity. The enzyme AMP-activated protein kinase (AMPK) is present in PVAT and is implicated in mediating the vascular effects of adiponectin. In this study, we investigated the effect of an obesogenic high fat diet (HFD) on aortic PVAT and whether any changes involved AMPK.Methods:Wild type Sv129 (WT) and AMPKα1 knockout (KO) mice aged 8 weeks were fed normal diet (ND) or HFD (42% kcal fat) for 12 weeks. Adiponectin production by PVAT was assessed by ELISA and AMPK expression studied using immunoblotting. Macrophages in PVAT were identified using immunohistochemistry and markers of M1 and M2 macrophage subtypes evaluated using real time-qPCR. Vascular responses were measured in endothelium-denuded aortic rings with or without attached PVAT. Carotid wire injury was performed and PVAT inflammation studied 7 days later.Key results:Aortic PVAT from KO and WT mice was morphologically indistinct but KO PVAT had more infiltrating macrophages. HFD caused an increased infiltration of macrophages in WT mice with increased expression of the M1 macrophage markersNos2andIl1band the M2 markerChil3. In WT mice, HFD reduced the anticontractile effect of PVAT as well as reducing adiponectin secretion and AMPK phosphorylation. PVAT from KO mice on ND had significantly reduced adiponectin secretion and no anticontractile effect and feeding HFD did not alter this. Wire injury induced macrophage infiltration of PVAT but did not cause further infiltration in KO mice.Conclusions:High-fat diet causes an inflammatory infiltrate, reduced AMPK phosphorylation and attenuates the anticontractile effect of murine aortic PVAT. Mice lacking AMPKα1 phenocopy many of the changes in wild-type aortic PVAT after HFD, suggesting that AMPK may protect the vessel against deleterious changes in response to HFD.
Pharmacology, Toxicology and Pharmaceutical Science
8
15%
Medicine and Dentistry
8
15%
Biochemistry, Genetics and Molecular Biology
8
15%
Agricultural and Biological Sciences
6
11%
Nursing and Health Professions
2
4%
Other
6
11%
Unknown
17
31%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 13 February 2018.
All research outputs
#14,374,920
of 23,023,224 outputs
Outputs from Frontiers in Physiology
#5,335
of 13,773 outputs
Outputs of similar age
#242,203
of 442,600 outputs
Outputs of similar age from Frontiers in Physiology
#131
of 307 outputs
Altmetric has tracked 23,023,224 research outputs across all sources so far. This one is in the 35th percentile – i.e., 35% of other outputs scored the same or lower than it.
So far Altmetric has tracked 13,773 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 7.6. This one has gotten more attention than average, scoring higher than 58% of its peers.
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We're also able to compare this research output to 307 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 53% of its contemporaries.
