Experimental drug helps obese mice lose fat without losing muscle

Experimental drug TOFA helped obese mice lose weight mainly by burning fat, without reducing their food intake or substantially diminishing their muscle mass, ERR reported.

Most weight-loss medicines work primarily by suppressing appetite and reducing the amount of food people eat. TOFA appears to work differently by helping the body use more energy from food and increasing overall energy expenditure.

In a study published in Science Advances, obese male mice given the compound lost an average of 18 percent of their body weight over four weeks, while their food intake remained unchanged. Most of the weight loss came from fat, while muscle mass and other fat-free body tissue were largely preserved.

The compound, known as 5-tetradecyloxy-2-furoic acid, or TOFA, was tested by a research team at the University of California, Berkeley. The researchers first fed the mice a high-fat diet to make them obese, then administered TOFA orally twice a day for four weeks.

Study leader Anders Näär, a metabolism biologist, said the mice’s food intake and physical activity remained unchanged, and their body temperature did not rise. However, their total energy expenditure increased by up to 18 percent.

TOFA did not make the mice more active or prevent them from absorbing calories from food. Instead, it changed how their bodies processed fat and used energy. The compound both slowed the production of new fat and helped cells absorb existing fat and burn it for energy.

Researchers do not yet know exactly what causes the additional energy expenditure. They initially expected to reproduce TOFA’s effects by combining two separate treatments, one to slow fat production and another to increase fat burning. However, the combination did not produce the same result, suggesting that having both effects in a single molecule may be important.

TOFA was first synthesised in the 1970s and has been used in laboratory research for years. Näär said its ability to activate fat-burning processes had probably existed all along, but researchers had not previously known to look for it.

The treatment also lowered blood glucose and insulin levels, improved glucose tolerance and reduced the amount of fat in the blood and liver. In other experiments, TOFA eased problems associated with fatty liver disease, including fat accumulation, inflammation and scarring.

Näär stressed that TOFA does not directly protect muscles. Because the mice continued eating normally, however, their weight loss came mainly from fat, avoiding the loss of fat-free body mass that often accompanies weight reduction.