Common Cancer Drugs Spark Weight Loss in Morbidly Obese Mice

Methotrexate and cyclophosphamide burn excessive dietary fat.

Morbidly obese mice administered 2 commonly-used cancer drugs experienced weight loss, despite the continual consumption of a high-fat diet.

In a study published in Oncotarget, the investigators administered the chemotherapy drugs methotrexate and cyclophosphamide to obese mice who ended up losing weight.

“We were surprised to observe that when morbidly obese mice were treated with certain cancer-fighting drugs, the drugs not only targeted their cancers, but also tended to spontaneously resolve their obesity—–even with undiminished gorging on a high-fat diet,” said investigator Peter Cohen, MD.

The results of the study showed that the multiple effects of the 2 chemotherapy agents worked together to expedite weight loss in mice. Similarly to chemotherapy’s ability to decrease red and white blood cell precursors transiently, methotrexate and cyclophosphamide depleted fat cell precursors, resulting in decreased fat storage.

“This meant that excessive dietary calories had to go somewhere else in the body instead, such as to the liver,” Cohen said.

The investigators found that the liver maintained a robust level of metabolic activity during treatment with methotrexate and cyclophosphamide. In regards to fat production and storage, however, it nearly shut down, according to the authors.

“Based on our composite data, it appears that methotrexate or cyclophosphamide can induce the livers of obese mice to burn off rather than accumulate excessive dietary fat,” investigator Sandra Gendler, PhD. “This results in desirable weight reduction instead of increased obesity, even with the continued caloric binging.”

More research needs to be done to see if the same outcome can be achieved in morbidly obese human patients.

“The ease with which this weight loss was achieved in mice—–even with continued caloric binging––is in stark contrast to the Herculean difficulties morbidly obese patients experience trying to preserve weight loss through dietary restraint,” Gendler said.

Future research will examine how these metabolic mechanisms could reduce the need for severe dietary constraints in morbidly obese individuals.