| Title |
AICAR ameliorates high-fat diet-associated pathophysiology in mouse and ex vivo models, independent of adiponectin
|
|---|---|
| Published in |
Diabetologia, February 2017
|
| DOI | 10.1007/s00125-017-4211-9 |
| Pubmed ID | |
| Authors |
Emma Börgeson, Ville Wallenius, Gulam H. Syed, Manjula Darshi, Juan Lantero Rodriguez, Christina Biörserud, Malin Ragnmark Ek, Per Björklund, Marianne Quiding-Järbrink, Lars Fändriks, Catherine Godson, Kumar Sharma |
| Abstract |
In this study, we aimed to evaluate the therapeutic potential of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), an activator of AMP-activated protein kinase, for ameliorating high-fat diet (HFD)-induced pathophysiology in mice. We also aimed to determine whether the beneficial effects of AICAR were dependent on adiponectin. Furthermore, human adipose tissue was used to examine the effect of AICAR ex vivo. Six-week-old male C57BL/6J wild-type and Adipoq (-/-) mice were fed a standard-fat diet (10% fat) or an HFD (60% fat) for 12 weeks and given vehicle or AICAR (500 μg/g) three times/week from weeks 4-12. Diet-induced pathophysiology was examined in mice after 11 weeks by IPGTT and after 12 weeks by flow cytometry and western blotting. Human adipose tissue biopsies from obese (BMI 35-50 kg/m(2)) individuals were incubated with vehicle or AICAR (1 mmol/l) for 6 h at 37°C, after which inflammation was characterised by ELISA (TNF-α) and flow cytometry. AICAR attenuated adipose inflammation in mice fed an HFD, promoting an M1-to-M2 macrophage phenotype switch, while reducing infiltration of CD8(+) T cells. AICAR treatment of mice fed an HFD partially restored glucose tolerance and attenuated hepatic steatosis and kidney disease, as evidenced by reduced albuminuria (p < 0.05), urinary H2O2 (p < 0.05) and renal superoxide levels (p < 0.01) in both wild-type and Adipoq (-/-) mice. AICAR-mediated protection occurred independently of adiponectin, as similar protection was observed in wild-type and Adipoq (-/-) mice. In addition, AICAR promoted an M1-to-M2 macrophage phenotype switch and reduced TNF-α production in tissue explants from obese human patients. AICAR may promote metabolic health and protect against obesity-induced systemic diseases in an adiponectin-independent manner. Furthermore, AICAR reduced inflammation in human adipose tissue explants, suggesting by proof-of-principle that the drug may reduce obesity-induced complications in humans. ClinicalTrials.gov NCT02322073. |
X Demographics
The data shown below were collected from the profiles of 22 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 5 | 23% |
| Canada | 3 | 14% |
| Ireland | 2 | 9% |
| Spain | 1 | 5% |
| Mexico | 1 | 5% |
| Cabo Verde | 1 | 5% |
| Unknown | 9 | 41% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 11 | 50% |
| Scientists | 8 | 36% |
| Practitioners (doctors, other healthcare professionals) | 3 | 14% |
Mendeley readers
The data shown below were compiled from readership statistics for 40 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 40 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 8 | 20% |
| Researcher | 6 | 15% |
| Professor > Associate Professor | 4 | 10% |
| Student > Master | 4 | 10% |
| Student > Bachelor | 3 | 8% |
| Other | 3 | 8% |
| Unknown | 12 | 30% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 6 | 15% |
| Agricultural and Biological Sciences | 6 | 15% |
| Biochemistry, Genetics and Molecular Biology | 3 | 8% |
| Immunology and Microbiology | 3 | 8% |
| Psychology | 2 | 5% |
| Other | 4 | 10% |
| Unknown | 16 | 40% |
Attention Score in Context
This research output has an Altmetric Attention Score of 12. 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 21 March 2018.
All research outputs
#2,746,281
of 23,321,213 outputs
Outputs from Diabetologia
#1,375
of 5,122 outputs
Outputs of similar age
#59,356
of 424,462 outputs
Outputs of similar age from Diabetologia
#30
of 58 outputs
Altmetric has tracked 23,321,213 research outputs across all sources so far. Compared to these this one has done well and is in the 88th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 5,122 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 23.0. This one has gotten more attention than average, scoring higher than 73% of its peers.
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