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Experimental antidiabetic drug ‘browns’ white fat in animal studies.

An experimental drug developed by QuatRx Pharmaceuticals causes loss of weight and fat in a mouse animal model in a new study from researchers at the Houston Methodist Research Institute.  Known as GC-1, the drug reportedly speeds up metabolism, or burning off, of fat cells.  The team state that GC-1 was observed dramatically increasing the metabolic rate, essentially converting white fat, which stores excess calories and is associated with obesity and metabolic disease, into a fat like calorie-burning brown fat.  The study results will be presented at the Endocrine Society’s 97th annual meeting in San Diego.

Until several years ago, scientists thought that only animals and human infants have energy-burning, ‘good’ brown fat.  It is now clear, that human adults do have brown fat, but appear to lose its calorie-burning activity over time.  The team explain that white adipose tissue, or fat, becomes a ‘metabolic villain’ when the body has too much of it. Previous studies show that people who have more brown fat have a reduced risk of obesity and diabetes with the medical community working on ways to ‘brown’ white fat, or convert it into brown fat.

The team state that GC-1 works by activating the receptors for thyroid hormone, which play a role in regulating metabolism, the body’s conversion of food into energy. Thyroid hormone receptors also help with adaptive thermogenesis, in which the body converts excess energy, or calories and fat, to heat.

The researchers tested the drug in hundreds of obese mice, both genetically obese and those with diet-induced obesity.

In the current study genetically obese mice lost weight and more than 50 percent of their fat mass in approximately two weeks.  Treated mice also showed antidiabetic effects, such as a sixfold improvement or increased insulin sensitivity which is an indicator of how well the body clears glucose from the bloodstream. The team state that mice with diet-induced obesity experienced similar improvements.  The drug also induced adaptive thermogenesis in fat cells isolated from mice. Cells grown in culture in a dish, as well as tissue samples taken from obese mice, showed evidence of white-fat browning.

The team state that the data demonstrate that GC-1 is a novel fat-browning agent that may have use in the treatment of obesity and metabolic disease.

The researchers stress that the drug has not yet undergone testing for weight loss in humans with GC-1 being tested in clinical trials for lowering cholesterol, under the name sobetirome.  The team state that the doses of sobetirome used in the cholesterol-lowering studies are much lower than what would be needed for weight loss.

Source:  Endocrine Society

Fat cell. Coloured scanning electron micrograph (SEM) of an adipocyte (fat cell, blue). Surrounding the adipocyte are white blood cells (red). Adipocytes store energy as an insulating layer of fat and the majority of the cell's volume is taken up by a large lipid (fat or oil) droplet. Fat accumulation starts with a few small lipid droplets (small blue blobs) which coalesce to make one large droplet. When mature, the adipocyte may be 10 or 20 times its original size. Magnification: x6000 when printed at 10 centimetres wide.  Credit: SCIENCE PHOTO LIBRARY.
Fat cell. Coloured scanning electron micrograph (SEM) of an adipocyte (fat cell, blue). Surrounding the adipocyte are white blood cells (red). Adipocytes store energy as an insulating layer of fat and the majority of the cell’s volume is taken up by a large lipid (fat or oil) droplet. Fat accumulation starts with a few small lipid droplets (small blue blobs) which coalesce to make one large droplet. When mature, the adipocyte may be 10 or 20 times its original size. Magnification: x6000 when printed at 10 centimetres wide. Credit: SCIENCE PHOTO LIBRARY.

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