09:59pm Tuesday 26 September 2017

Brain mechanism of action discovered for obesity suppressing drug

GLP-1 mimicking substances are a relatively new class of drugs used to regulate blood sugar in patients with type 2 diabetes. Examples of GLP-1 mimicking drugs currently available on the market are Byetta och Victoza. They can help in regulation of blood sugar by increasing the amount of insulin available after a meal.

GLP-1 is actually naturally made in the intestine after food has entered the intestinal tract.

Suppress appetite

Importantly, it has been known for several years that these drugs suppress appetite and obesity to a certain extent, as the patients lose on average about 3 kg body weight. These drugs are now in clinical trials for treatment of obesity in the absence of type 2 diabetes.

International research team

An international team of scientists led by researchers from Sahlgrenska Academy have made a surprising finding that sheds light on how the GLP-1 mimicking drugs can help in appetite suppression and body weight reduction.

It turns out that GLP-1 allowed to enter the brain stimulated the production of two immune modulating substances, interleukin-1 and interleukin-6, in important areas of the brain that are known to control food intake and metabolism.

Key to beneficial effects

These two substances are key to the beneficial effects of GLP-1, since when scientist blocked them either by using pharmacology or genetics in rats and mice, GLP-1 was no longer able to suppress appetite or body weight.

“Although these drugs have been on the market for almost 10 years the brain circuits and neurochemicals engaged by GLP-1 mimicking drugs to reduce appetite and body weight are still poorly understood, we are happy to come a bit closer to understanding how these drugs may affect the brain” says Karolina Skibicka, senior author of the study.

“It is perhaps surprising that two immune modulating hormones are acting in the brain of healthy rats and mice to mediate the anti-obesity effect of this widely used group of drugs.”, says John-Olov Jansson, who also participated in the study.

Help reduce body weight

Though it should be mentioned that Sahlgrenska scientists and other international research groups have previously shown that interleukin-1 and interleukin-6 are special among immune modulators and in some circumstances can help reduce body weight without activating the immune system in an unhealthy way.

Information about the mechanisms behind the effects of GLP-1 mimicking drugs may lead to new strategies and drugs for treatment of obesity. The number of patients with obesity is increasing at an alarming rate worldwide, and there is an urgent need for new pharmacologic treatments.

Original article:Glucagon-like peptide 1 receptor induced suppression of food intake, and body weight is mediated by central IL-1 and IL-6. Shirazi R, Palsdottir V, Collander J, Anesten F, Vogel H, Langlet F, Jaschke A, Schürmann A, Prévot V, Shao R, Jansson JO, Skibicka KP.

Proc Natl Acad Sci U S A. 2013 Sep 18. [Epub ahead of print] PMID: 24048027

Link to article: 
http://www.pnas.org/content/110/40/16199.long

Contact:
Karolina Skibicka, Assistant Professor at the Sahlgrenska Academy, Gothenburg University, +46 317863589, +46 702 918835,  Karolina.Skibicka@neuro.gu.se

John-Olov Jansson, Professor at the Sahlgrenska Academy, Gothenburg University, +46 739-011122, joj@neuro.gu.se
 

BY: Elin Lindström Claessen


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