| First Author | Winn NC | Year | 2019 |
| Journal | Am J Physiol Endocrinol Metab | Volume | 316 |
| Issue | 2 | Pages | E156-E167 |
| PubMed ID | 30512987 | Mgi Jnum | J:274418 |
| Mgi Id | MGI:6283313 | Doi | 10.1152/ajpendo.00259.2018 |
| Citation | Winn NC, et al. (2019) Estrogen receptor-alpha signaling maintains immunometabolic function in males and is obligatory for exercise-induced amelioration of nonalcoholic fatty liver. Am J Physiol Endocrinol Metab 316(2):E156-E167 |
| abstractText | The role of estrogen receptor-alpha (ERalpha) signaling in immunometabolic function is established in females. However, its necessity in males, while appreciated, requires further study. Accordingly, we first determined whether lower metabolic function in male mice compared with females is related to reduced ERalpha expression. ERalpha protein expression in metabolically active tissues was lower in males than in females, and this lower expression was associated with worse glucose tolerance. Second, we determined whether ERalpha is required for optimal immunometabolic function in male mice consuming a chow diet. Despite lower expression of ERalpha in males, its genetic ablation (KO) caused an insulin-resistant phenotype characterized by enhanced adiposity, glucose intolerance, hepatic steatosis, and metaflammation in adipose tissue and liver. Last, we determined whether ERalpha is essential for exercise-induced metabolic adaptations. Twelve-week-old wild-type (WT) and ERalpha KO mice either remained sedentary (SED) or were given access to running wheels (WR) for 10 wk while fed an obesogenic diet. Body weight and fat mass were lower in WR mice regardless of genotype. Daily exercise obliterated immune cell infiltration and inflammatory gene transcripts in adipose tissue in both genotypes. In the liver, however, wheel running suppressed hepatic steatosis and inflammatory gene transcripts in WT but not in KO mice. In conclusion, the present findings indicate that ERalpha is required for optimal immunometabolic function in male mice despite their reduced ERalpha protein expression in metabolically active tissues. Furthermore, for the first time, we show that ERalpha signaling appears to be obligatory for exercise-induced prevention of hepatic steatosis. |
