| First Author | Ribas V | Year | 2016 |
| Journal | Sci Transl Med | Volume | 8 |
| Issue | 334 | Pages | 334ra54 |
| PubMed ID | 27075628 | Mgi Jnum | J:246223 |
| Mgi Id | MGI:5923320 | Doi | 10.1126/scitranslmed.aad3815 |
| Citation | Ribas V, et al. (2016) Skeletal muscle action of estrogen receptor alpha is critical for the maintenance of mitochondrial function and metabolic homeostasis in females. Sci Transl Med 8(334):334ra54 |
| abstractText | Impaired estrogen receptor alpha (ERalpha) 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 ERalpha expression in muscle is associated with glucose intolerance and adiposity in women and female mice. To test this relationship, we generated muscle-specific ERalpha 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, ERalpha 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 ERalpha in the preservation of mitochondrial health and insulin sensitivity as a defense against metabolic disease in women. |
