| Title |
Hepatocyte glutathione peroxidase-1 deficiency improves hepatic glucose metabolism and decreases steatohepatitis in mice
|
|---|---|
| Published in |
Diabetologia, September 2016
|
| DOI | 10.1007/s00125-016-4084-3 |
| Pubmed ID | |
| Authors |
Troy L. Merry, Melanie Tran, Garron T. Dodd, Salvatore P. Mangiafico, Florian Wiede, Supreet Kaur, Catriona L. McLean, Sofianos Andrikopoulos, Tony Tiganis |
| Abstract |
In obesity oxidative stress is thought to contribute to the development of insulin resistance, non-alcoholic fatty liver disease and the progression to non-alcoholic steatohepatitis. Our aim was to examine the precise contributions of hepatocyte-derived H2O2 to liver pathophysiology. Glutathione peroxidase (GPX) 1 is an antioxidant enzyme that is abundant in the liver and converts H2O2 to water. We generated Gpx1 (lox/lox) mice to conditionally delete Gpx1 in hepatocytes (Alb-Cre;Gpx1 (lox/lox)) and characterised mice fed chow, high-fat or choline-deficient amino-acid-defined (CDAA) diets. Chow-fed Alb-Cre;Gpx1 (lox/lox) mice did not exhibit any alterations in body composition or energy expenditure, but had improved insulin sensitivity and reduced fasting blood glucose. This was accompanied by decreased gluconeogenic and increased glycolytic gene expression as well as increased hepatic glycogen. Hepatic insulin receptor Y1163/Y1163 phosphorylation and Akt Ser-473 phosphorylation were increased in fasted chow-fed Alb-Cre;Gpx1 (lox/lox) mice, associated with increased H2O2 production and insulin signalling in isolated hepatocytes. The enhanced insulin signalling was accompanied by the increased oxidation of hepatic protein tyrosine phosphatases previously implicated in the attenuation of insulin signalling. High-fat-fed Alb-Cre;Gpx1 (lox/lox) mice did not exhibit alterations in weight gain or hepatosteatosis, but exhibited decreased hepatic inflammation, decreased gluconeogenic gene expression and increased insulin signalling in the liver. Alb-Cre;Gpx1 (lox/lox) mice fed a CDAA diet that promotes non-alcoholic steatohepatitis exhibited decreased hepatic lymphocytic infiltrates, inflammation and liver fibrosis. Increased hepatocyte-derived H2O2 enhances hepatic insulin signalling, improves glucose control and protects mice from the development of non-alcoholic steatohepatitis. |
X Demographics
The data shown below were collected from the profiles of 4 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 States | 1 | 25% |
| Canada | 1 | 25% |
| Unknown | 2 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 50% |
| Scientists | 1 | 25% |
| Practitioners (doctors, other healthcare professionals) | 1 | 25% |
Mendeley readers
The data shown below were compiled from readership statistics for 39 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 3% |
| Unknown | 38 | 97% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 7 | 18% |
| Student > Master | 6 | 15% |
| Student > Postgraduate | 2 | 5% |
| Student > Doctoral Student | 2 | 5% |
| Student > Bachelor | 2 | 5% |
| Other | 6 | 15% |
| Unknown | 14 | 36% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 6 | 15% |
| Biochemistry, Genetics and Molecular Biology | 5 | 13% |
| Pharmacology, Toxicology and Pharmaceutical Science | 3 | 8% |
| Sports and Recreations | 3 | 8% |
| Medicine and Dentistry | 3 | 8% |
| Other | 4 | 10% |
| Unknown | 15 | 38% |
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 21 November 2016.
All research outputs
#13,743,461
of 23,299,593 outputs
Outputs from Diabetologia
#4,302
of 5,118 outputs
Outputs of similar age
#170,795
of 322,505 outputs
Outputs of similar age from Diabetologia
#64
of 80 outputs
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