The Cancer Drug That Could Also Fight Obesity
A cancer-fighting compound has been found to also reduce fat in obese mice and could potentially help 93 million obese Americans fight their fat. Published in Science Translational Medicine, Eric Prossnitz and his team at the University of New Mexico, USA discovered that the G-1 compound currently in clinical trials for breast cancer can also reduce fat and eliminate diabetes in mice.
Obesity affects nearly 25% of adults in the UK and 40% of adults in the United States. A range of complications are associated with it, such as Type 2 diabetes, heart disease, high blood pressure, stroke, and certain cancers (breast, colon and endometrial). Sometimes drugs and surgery are offered to help people with obesity, but making lifestyle changes are highly recommended.
The researchers studied GPER, a G protein-coupled oestrogen receptor that is activated by the drug G-1. Some breast cancer drugs block oestrogen receptors in the cell’s nucleus and in turn activate GPER on cell membranes. The team’s previous studies showed that GPER could play a role in drug resistance in breast cancer cells, and wanted to find out how the G-1 protein can affect non-cancerous cells when oestrogen is lacking.
Women produce oestrogen at levels far higher than men. Oestrogen levels in women decrease during menopause, and postmenopausal women are at a higher risk of developing obesity, diabetes, high blood pressure and heart disease. The team studied mice with low oestrogen levels to see whether the G-1 compound may affect metabolism in postmenopausal woman.
They showed that female mice with low oestrogen gained weight rapidly, quickly becoming obese and diabetic even on a normal diet. When they were treated with G-1, the obese female mice lost weight and their diabetes was eliminated. The G-1 compound allowed the mice to use the calories as fuel rather than storing them as fat, effectively changing their metabolism.
Male mice naturally have low levels of oestrogen and became obese and diabetic on a high-fat diet. Some of the male mice were treated with G-1, but they didn’t lose weight. They didn’t gain any additional weight either and their diabetes improved, becoming metabolically healthier. The researchers suggest that G-1 has separate effects on obesity and diabetes, and sex differences play a role in the effect of the drug or GPER signalling in cells.
G-1 was also found to increase energy expenditure in brown fat cells, which generate heat instead of storing excess calories as fat.
Prossnitz and his team are planning to study how GPER signalling causes cellular changes to increase the amount of energy used, and are currently planning preclinical studies to use G-1 to fight fat in obese people.