| Title |
Intervention with a caspase-1 inhibitor reduces obesity-associated hyperinsulinemia, non-alcoholic steatohepatitis and hepatic fibrosis in LDLR−/−.Leiden mice
|
|---|---|
| Published in |
International Journal of Obesity, May 2016
|
| DOI | 10.1038/ijo.2016.74 |
| Pubmed ID | |
| Authors |
M C Morrison, P Mulder, K Salic, J Verheij, W Liang, W van Duyvenvoorde, A Menke, T Kooistra, R Kleemann, P Y Wielinga |
| Abstract |
Non-alcoholic steatohepatitis (NASH) is a serious liver condition, closely associated with obesity and insulin resistance. Recent studies have suggested an important role for inflammasome/caspase-1 in the development of NASH, but the potential therapeutic value of caspase-1 inhibition remains unclear. Therefore, we aimed to investigate the effects of caspase-1 inhibition in the ongoing disease process, to mimic the clinical setting. To investigate effects of caspase-1 inhibition under therapeutic conditions, male LDLR-/-.Leiden mice were fed a high-fat diet (HFD) for 9 weeks to induce a pre-diabetic state before start of treatment. Mice were then continued on HFD for another 12 weeks, without (HFD) or with (HFD-YVAD) treatment with the caspase-1 inhibitor Ac-YVAD-cmk (40 mg/kg/day). 9 weeks of HFD feeding resulted in an obese phenotype, with obesity-associated hypertriglyceridemia, hypercholesterolemia, hyperglycemia, and hyperinsulinemia. Treatment with Ac-YVAD-cmk did not affect further body weight gain or dyslipidaemia, but did attenuate further progression of insulin resistance. Histopathological analysis of livers clearly demonstrated prevention of NASH development in HFD-YVAD mice: livers were less steatotic and neutrophil infiltration was strongly reduced. In addition, caspase-1 inhibition had a profound effect on hepatic fibrosis, as assessed by histological quantification of collagen staining and gene expression analysis of fibrosis-associated genes Col1a1, Acta2, and Tnfa. Intervention with a caspase-1 inhibitor attenuated the development of NASH, liver fibrosis and insulin resistance. Our data support the importance of inflammasome/caspase-1 in the development of NASH and demonstrate that therapeutic intervention in the already ongoing disease process is feasible.International Journal of Obesity accepted article preview online, 28 April 2016. doi:10.1038/ijo.2016.74. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Brazil | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 44 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 44 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 9 | 20% |
| Researcher | 6 | 14% |
| Student > Bachelor | 4 | 9% |
| Other | 3 | 7% |
| Student > Master | 2 | 5% |
| Other | 6 | 14% |
| Unknown | 14 | 32% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 8 | 18% |
| Biochemistry, Genetics and Molecular Biology | 7 | 16% |
| Medicine and Dentistry | 4 | 9% |
| Immunology and Microbiology | 2 | 5% |
| Nursing and Health Professions | 1 | 2% |
| Other | 5 | 11% |
| Unknown | 17 | 39% |
Attention Score in Context
This research output has an Altmetric Attention Score of 4. 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 07 March 2023.
All research outputs
#7,036,222
of 23,495,502 outputs
Outputs from International Journal of Obesity
#2,422
of 4,371 outputs
Outputs of similar age
#109,862
of 340,255 outputs
Outputs of similar age from International Journal of Obesity
#44
of 63 outputs
Altmetric has tracked 23,495,502 research outputs across all sources so far. This one has received more attention than most of these and is in the 69th percentile.
So far Altmetric has tracked 4,371 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 24.2. This one is in the 44th percentile – i.e., 44% of its peers scored the same or lower than it.
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