Fat pill for mice

Tuesday July 14 2009

A pill "could reduce body fat by half in a week", reports the Daily Mail . It said that scientists are working on an anti-obesity pill which, at least in mice, has been shown to reduce body weight by a quarter, and fat content by 42% in just seven days. The newspaper also said it could take a decade for a potential drug to be developed for use in patients.

This study was in mice and more research is needed before the drug can be tested in humans. Human trials are likely to be several years away, and these findings must be interpreted in the context of early, animal research. To date, single drugs have not been very successful at treating obesity, so this is an important finding in that a single agent can simultaneously activate more than one mechanism to reduce body weight.

Where did the story come from?

The research was carried out by Dr Jonathan Day and colleagues from Indiana University, the University of Cincinnati, Marcadia Biotech, the University of Kentucky College of Medicine, and the University of Toronto. The study was published in the peer-reviewed scientific journal Nature Chemical Biology .

What kind of scientific study was this?

This laboratory study investigated the combined effects of two different hormones involved in glucose metabolism (glucagon and GLP-1) on weight in mice. Glucagon and GLP-1 are peptides (compounds of amino acids). Glucagon is produced by the pancreas when blood glucose is low and raises blood levels by encouraging glycogen stored in the liver to convert to glucose. GLP-1 has an opposite effect, and reduces blood glucose through a variety of different biochemical processes, such as increasing insulin synthesis in the pancreas.

The researchers manipulated glucagon peptides at a molecular level, adding to them some of the characteristics and actions of GLP-1. The new peptides had properties of both glucagon and GLP-1 and could last longer within the body than glucagon peptides.

The modified glucagon peptides were then injected once a week into diet-induced obese mice (fed on a high-sugar and high-fat diet). The experiment was repeated in obese mice that were given weekly injections for a month. The experiments were repeated in rats.

What were the results of the study?

The injections of one particular modified glucagon peptide  – ‘the balanced lactam-based co-agonist peptide’ – reduced body weight in mice by 26% over a week. This peptide was called ‘balanced’ because as a modified molecule it demonstrated properties of both native glucagon and GLP-1 hormones in their unmodified forms. Fat mass in particular was reduced by 42% with this peptide compared to 2.3% in mice injected with a saline control.

An unbalanced form (having the properties of native GLP-1 but reduced glucagon activity) also had effects on weight, but they were not as pronounced, with a 22% fat reduction from the start of the study. Blood glucose reduced with both of these peptides compared with controls.

When researchers varied the doses of each form that the mice were given, they found a dose-response reduction in body weight and blood glucose. Importantly, there was no evidence of hypo- or hyperglycemia (i.e. acute reduced or high blood glucose), in spite of the effects of these compounds.

In the month-long study, energy expenditure was increased in mice given the lactam-based peptide. In addition, fat mass was reduced by 63%, and body weight by 28% compared to the beginning of the study. As expected, blood glucose levels decreased during the treatment period. The peptides had other effects on the mice, such as reduced cholesterol in mice treated for 27 days.

What interpretations did the researchers draw from these results?

The study found that a manipulated peptide with a balanced co-agonism (i.e. essentially combining the effects of both glucagon and GLP-1 in glucose metabolism) was particularly effective in reducing weight, particularly fat mass, and improving glucose metabolism. They conclude that further studies will be needed to determine the optimum balance of activity of these two enzymes.

What does the NHS Knowledge Service make of this study?

The study raises new questions and opportunities to advance pharmacological treatments for obesity, but the application to the health of humans remains a long way off. The compounds will undergo further animal testing before they can be tried in humans. Even if they do reach human trials, there is no guarantee that a pill produced from this research would cause a similar dramatic weight loss for people with obesity.

To date, single drugs are not very successful for people with obesity, so the finding that a single agent can simultaneously activate more than one mechanism to reduce body weight is an important one. The researchers say that other molecules could be combined into a single co-agonist. However, this is still an early study in animals, and these claims must be interpreted within this context.

Analysis by Bazian
Edited by NHS Choices