| First Author | Stout MB | Year | 2017 |
| Journal | J Gerontol A Biol Sci Med Sci | Volume | 72 |
| Issue | 1 | Pages | 3-15 |
| PubMed ID | 26809497 | Mgi Jnum | J:275098 |
| Mgi Id | MGI:6305920 | Doi | 10.1093/gerona/glv309 |
| Citation | Stout MB, et al. (2017) 17alpha-Estradiol Alleviates Age-related Metabolic and Inflammatory Dysfunction in Male Mice Without Inducing Feminization. J Gerontol A Biol Sci Med Sci 72(1):3-15 |
| abstractText | Aging is associated with visceral adiposity, metabolic disorders, and chronic low-grade inflammation. 17alpha-estradiol (17alpha-E2), a naturally occurring enantiomer of 17beta-estradiol (17beta-E2), extends life span in male mice through unresolved mechanisms. We tested whether 17alpha-E2 could alleviate age-related metabolic dysfunction and inflammation. 17alpha-E2 reduced body mass, visceral adiposity, and ectopic lipid deposition without decreasing lean mass. These declines were associated with reductions in energy intake due to the activation of hypothalamic anorexigenic pathways and direct effects of 17alpha-E2 on nutrient-sensing pathways in visceral adipose tissue. 17alpha-E2 did not alter energy expenditure or excretion. Fasting glucose, insulin, and glycosylated hemoglobin were also reduced by 17alpha-E2, and hyperinsulinemic-euglycemic clamps revealed improvements in peripheral glucose disposal and hepatic glucose production. Inflammatory mediators in visceral adipose tissue and the circulation were reduced by 17alpha-E2. 17alpha-E2 increased AMPKalpha and reduced mTOR complex 1 activity in visceral adipose tissue but not in liver or quadriceps muscle, which is in contrast to the generalized systemic effects of caloric restriction. These beneficial phenotypic changes occurred in the absence of feminization or cardiac dysfunction, two commonly observed deleterious effects of exogenous estrogen administration. Thus, 17alpha-E2 holds potential as a novel therapeutic for alleviating age-related metabolic dysfunction through tissue-specific effects. |
