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
(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.
 Guillaume M, Handgraaf S, Fabre A et al. Selective activation of estrogen receptor Î± 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