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Asthma drug reverses obesity and diabetes in mice

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February 13, 2013

The obese mouse on the right was fed a high-fat diet. The mouse on the left was fed the sa...

The obese mouse on the right was fed a high-fat diet. The mouse on the left was fed the same diet but is a normal weight after receiving amlexanox (Photo: Shannon Reilly)

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Researchers at the University of Michigan’s Life Sciences Institute have found that amlexanox, an off-patent drug used to treat asthma and canker sores, can also reduce obesity, diabetes and fatty liver disease in mice.

The team led by Life Sciences Institute director, Alan Saltiel, focused on the impact that the drug amlexanox has on the genes IKKE and TBK1 in mice. This followed on from research the Saltiel lab published in Cell Magazine in 2009 suggesting a link between the genes, obesity, insulin resistance and diabetes. Saltiel maintains IKKE and TBK1 play a crucial role maintaining "metabolic balance."

Professor Saltiel explains that IKKE and TBK1 are part of a process of inflammation linked to obesity and insulin resistance, the condition that precedes Type 2 diabetes.

“The basic story is that IKKE and TBK1 are elevated in obesity due to the generation of inflammation, and in turn are involved in repressing adaptive energy expenditure and producing insulin resistance,’’ Professor Saltiel told Gizmag.

“Thus, we think that these genes play a "counter-inflammatory" role, keeping inflammation at a low grade, sustained level, without allowing resolution, and preserving energy storage in fat and liver.”

Saltiel says this might explain why some people struggle to lose weight. “One of the reasons that diets are so ineffective in producing weight loss for some people is that their bodies adjust to the reduced calories by also reducing their metabolism so that they are ‘defending their body weight’.’’

Based on that research, the next step was to find compounds that would inhibit the expression of IKKE and TBK1. After some high-throughput chemical screening at the Institute’s Center for Chemical Genomics, Saltiel and his team identified amlexnox – a drug that has been used to treat asthma in Japan for the last 25 years and to treat canker sores in the United States.

They tested the drug on both genetic and dietary-induced obese mice, finding that it elevated energy expenditure in the mice, increasing the heat in their bodies and producing weight loss. In addition to treading obesity, it reversed related metabolic problems such as diabetes and fatty liver.

“These studies tell us that, at least in mice, the IKKE/TBK1 pathway plays an important role in defending body weight by increasing storage and decreasing burning of calories, and that by inhibiting that pathway with a compound, we can increase metabolism and induce weight loss, reverse diabetes and reduce fatty liver," says Saltiel.

Saltiel is now working with University of Michigan clinical trial specialists to test whether the drug will have the same impact on obese and diabetic humans as it did on mice. Clinical studies are planned for later this year.

“I have no idea whether or not it will work in patients, but we'll find out,’’ says Saltiel.

There is however room for optimism as amlexanox has been found to be safe for patients, and humans also have the same genetic pathways as mice. Saltiel is also working with medicinal chemists at the university to develop a new compound based on the drug that would optimize its formula.

The research was supported by the National Institutes of Health, the Michigan Diabetes Research and Training Center, the Michigan Institute for Clinical and Health Research, and the Nathan Shock Center in the Basic Biology of Aging.

The findings have been published in the journal Nature Medicine

Source: University of Michigan

About the Author
Leon Gettler An award winning author and freelance journalist with a strong background in newspapers, magazines and podcasts, Leon is passionately drawn to all things innovative and unknown with a deep interest in telecommunications, environmental technology and design. When not indulging his passion for reading and writing, he can be found memorizing lines immortalized by Gerry Mulligan on baritone sax. He lives in Melbourne, Australia.   All articles by Leon Gettler
4 Comments

When treating someone for obesity with prescription drugs, would the doctor stop prescribing when the patient gets down to a level of "somewhat overweight and out of shape but not obese"? If not--if they treat you down to your ideal weight--wouldn't it cause people who want to lose 10 pounds to figure they need to fatten up to the minimum body mass index score to be considered obese in order to gain access to medical help? That seems like the biggest problem of considering one type of weight loss a medical issue and one the other type a lifestyle/health issue.

Snake Oil Baron
13th February, 2013 @ 07:40 pm PST

Not everyone that is considered to be overweight has a eating disorder or a propensity to consume inappropriate food items in large quantities. We have all observed people that are very overweight eating things that they should not and in quantities that are inappropriate. This might finally be the answer for those people that fall into the other category of which I am one of them.

delcirose
14th February, 2013 @ 09:41 am PST

Baron: if someone is within 10 pounds of being obese, and the treatment will help them, then I don't see anything wrong with them seeking medical help. However, it may be that their doc will recommend that they use other less risky methods if they are close to the line (which is pretty low for muscular people, all things considered).

Charles Bosse
15th February, 2013 @ 06:34 am PST

there are already half a dozen of drugs that induce pound loss ( one of those is amphetamine) and every one of them has big contraindication or rebound effects...and every one of them reduces insuline resistance, fats in the blood and hypertension ( this triad is called metabolic syndrome) .

Facebook User
15th February, 2013 @ 10:56 pm PST
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