Shutterstock.com
In addition to its antagonistic effects on breast cancer proliferation through oestrogen-receptor modulation, tamoxifen is known to have complex metabolic effects. However, the underlying mechanisms are not well characterised.
To explore, researchers gave mice either tamoxifen or placebo and fed them a high-fat diet (HFD) between 6 and 12 weeks of life.
They found that tamoxifen prevented the HFD-induced weight gain, fat mass accumulation, glucose intolerance, insulin resistance and steatosis seen in placebo-treated mice. Using transgenic mice, they found evidence that the drug can independently exert these protective metabolic effects through two different oestrogen-receptor pathways. This contrasts with uterine or breast cancer proliferation, which requires concomitant activation of both pathways.
Reporting in the American Journal of Pathology
[1]
(online, 11 May 2017), the team says the results could inform the development of treatments for obesity-related complications by selectively targeting oestrogen-receptor pathways.
References
[1] Guillaume M, Handgraaf S, Fabre A et al. Selective activation of estrogen receptor α activation function-1 is sufficient to prevent obesity, steatosis, and insulin resistance in mouse. Am J Pathol 2017; 187:1273–1287. doi: 10.1016/j.ajpath.2017.02.013
