Transgenic Mice Could Solve The Obesity Epidemic

By tweaking an enzyme in mice, researchers expected to get rodents with low cholesterol, but fatty livers. Instead they found a switch which might be a weight loss miracle.

The researchers from the University of Alberta bred a mouse lacking a single enzyme that's associated with fat metabolism — triacylglycerol hydrolase (TGH). TGH is partly responsible for releasing triglycerides from the liver where they go on to form very low-density lipoproteins (VLDLs), which are considered "bad" cholesterol. The scientists thought that breeding a mouse deficient in TGH would have fewer VLDLs, and instead found the mice that not only had lower cholesterol, but also system wide metabolic improvement — seemingly without downside.

The researchers hypothesized that removing the TGH would mean the more fat would build up in the liver, as the mechanism by which the fat was released was missing. Instead of getting tiny rodent foie gras, the triglycerides were burned almost immediately rather than being stored, and the liver compensated by synthesizing less fat. The rodents ate more, but also expended more energy, and showed no change in body weight compared to their normal cousins.

Said Dr. Richard Lehner of the University of Alberta:

"It was a surprising and unexpected finding. With this gene deleted, not only was there a decline in very low-density lipoproteins in the whole mouse, it also affected metabolism in fat tissue. The insulin-secreting cells became smaller, suggesting that they didn't have to work as hard to secrete insulin, and the mice became more insulin sensitive."

The interesting thing? Drugs already exist to block TGH in the human body. While more research needs to be done about the systemic effects of blocking TGH, how specific these drugs are, and if diet alters the way the liver functions in these mice, but it's an important step towards understanding how the body deals with fat and cholesterol. Who knows, we may even get a drug that helps you lose weight without utterly horrible side effects.

Results published in Cell Metabolism
Image of an ob/ob mouse next to a normal mouse.