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| Status |
Public on Nov 01, 2019 |
| Title |
Role of Mineralocorticoid Receptor (Nr3c2) in Adipogenesis and Obesity in Male Mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Increased visceral adiposity and hyperglycemia, two characteristics of metabolic syndrome, are also present in conditions of excess glucocorticoids (GCs). GCs are hormones thought to act primarily via the glucocorticoid receptor (GR). GCs are commonly prescribed for inflammatory disorders, yet their use is limited due to many adverse metabolic side effects. In addition to GR, GCs also bind the mineralocorticoid receptor (MR), but there are many conflicting studies as to the exact role of MR in metabolic disease. Using MR knockout mice (MRKO), we find that both white and brown adipose depots form normally when compared to wild-type mice at P5. We created mice with adipocyte-specific deletion of MR (FMRKO) to better understand the role of MR in metabolic dysfunction. Treatment of mice with excess GCs for 4 weeks, via corticosterone in drinking water, induced increased fat mass and glucose intolerance to similar levels in FMRKO and floxed-control mice. Separately, when fed a high-fat diet for 16 weeks, FMRKO mice had reduced body weight, fat mass, and hepatic steatosis, relative to floxed-control mice. Decreased adiposity likely resulted from increased energy expenditure since food intake was not different. RNA sequencing analysis revealed decreased enrichment of genes associated with adipogenesis in inguinal white adipose of FMRKO mice. Differentiation of mouse embryonic fibroblasts (MEFs), showed modestly impaired adipogenesis in MRKO MEFs compared to wild-type, but this was rescued upon the addition of peroxisome proliferator-activated receptor gamma (PPARγ) agonist or PPARγ overexpression. Collectively, these studies provide further evidence supporting the potential value of MR as a therapeutic target for conditions associated with metabolic syndrome.
Method (Chow): At six weeks of age mice were maintained on a chow diet (PicoLab® Rodent Diet 20 5053* [20% protein]) for 16 weeks
Method (High Fat Diet): 6 week-old mice were fed ab libitum with Teklad TD.88137 (21.2% fat [42% kcal fat], 48.5% carbohydrate [34% sucrose by weight], 17.3% protein, and 0.2% cholesterol by weight) for 16 weeks
Method (Corticosterone): 10-11-week-old mice were administered corticosterone via drinking water (100 μg/mL) for 4 weeks, while maintained on a chow diet
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| Overall design |
Examination of inguinal white adipose from Nr3c2-floxed-control (control) and Nr3c2-floxed Adipoq-Cre+ (fat-specific mineralocorticoid receptor knockout, FMRKO) mice on chow diet, high fat diet, or corticosterone-treatment (n=4/group)
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| Contributor(s) |
Harris CA, Ferguson D |
| Citation |
Daniel Ferguson, Irina Hutson, Eric Tycksen, Terri A Pietka, Kevin Bauerle, Charles A Harris, Role of Mineralocorticoid Receptor in Adipogenesis and Obesity in Male Mice, Endocrinology, , bqz010, https://0-doi-org.brum.beds.ac.uk/10.1210/endocr/bqz010
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| Submission date |
Oct 09, 2019 |
| Last update date |
Jan 31, 2020 |
| Contact name |
Charles A Harris |
| E-mail(s) |
harrisc@wustl.edu
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| Phone |
3143623802
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| Organization name |
Washington University School of Medicine in St. Louis
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| Department |
Department of Medicine
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| Lab |
Harris Lab
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| Street address |
660 S. Euclid Ave
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| City |
St Louis |
| State/province |
MO |
| ZIP/Postal code |
63110 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (24)
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| Relations |
| BioProject |
PRJNA576638 |
| SRA |
SRP224951 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE138632_RAW.tar |
64.3 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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