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| Status |
Public on Sep 08, 2016 |
| Title |
The ERα Transcriptome |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Impaired estrogen receptor α (ERα) action promotes obesity and metabolic dysfunction in humans and mice; however, the mechanisms underlying these phenotypes remain unknown. Considering that skeletal muscle is a primary tissue responsible for glucose disposal and oxidative metabolism, we established that reduced ERα expression in muscle is associated with glucose intolerance and adiposity in women and female mice. To test this relationship, we generated muscle-specific ERα knockout (MERKO) mice. Impaired glucose homeostasis and increased adiposity were paralleled by diminished muscle oxidative metabolism and bioactive lipid accumulation in MERKO mice. Aberrant mitochondrial morphology, overproduction of reactive oxygen species, and impairment in basal and stress-induced mitochondrial fission dynamics, driven by imbalanced protein kinase A–regulator of calcineurin 1–calcineurin signaling through dynamin-related protein 1, tracked with reduced oxidative metabolism in MERKO muscle. Although muscle mitochondrial DNA (mtDNA) abundance was similar between the genotypes, ERα deficiency diminished mtDNA turnover by a balanced reduction in mtDNA replication and degradation. Our findings indicate the retention of dysfunctional mitochondria in MERKO muscle and implicate ERα in the preservation of mitochondrial health and insulin sensitivity as a defense against metabolic disease in women.
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| Overall design |
Quadriceps mRNA profiles of 20-week old wild type (WT) and muscle-specific ERα knockout (MERKO) mice were generated by deep sequencing, in triplicate, using Illumina HiSeq 2000.
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| Contributor(s) |
Hevener A |
| Citation missing |
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| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| K01 DK060484 |
The Role of PPAR-gamma Expression on Insulin Action: The Role of PPARgamma Expression on Insulin Action |
THE REGENTS OF THE UNIV. OF CALIF., UNIV. OF CALIF., SAN DIEGO |
HEVENER |
| R21 DK073227 |
The impact of PPAR-gamma and estrogen receptor crosstalk on insulin action |
UNIVERSITY OF CALIFORNIA LOS ANGELES |
Hevener |
| U24 DK097748 |
A Hub for the Nuclear Receptor Signaling Atlas1: A Hub for the Nuclear Receptor Signaling Atlas1: BD2K: INTEROPERABILITY OF NURSA WITH PHARMGKB AND DKNET: Expansion of NURSA Transcriptomine Annotation |
BAYLOR COLLEGE OF MEDICINE |
O'MALLEY |
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| |
| Submission date |
Sep 07, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Calvin Pan |
| Organization name |
UCLA
|
| Street address |
675 Charles Young Dr South
|
| City |
Los Angeles |
| ZIP/Postal code |
90095 |
| Country |
USA |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA342120 |
| SRA |
SRP087440 |
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