New targets for the event of a drug therapy for weight problems and kind 2 diabetes

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GIP or the double agonist GP-1 / GIP require the GIP receptor in the brain in order to reduce body weight and food intake. Photo credit: Helmholtz Zentrum München

The GIP receptor in the central nervous system plays a crucial role in regulating body weight and food intake. This is shown by a current study by the Helmholtz Zentrum München, ETH Zurich and the German Center for Diabetes Research (DZD). The study, now published in Cell Metabolism, identifies new targets for developing drug treatments for obesity and type 2 diabetes.

Dual agonists targeting the receptors for glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are promising new drug candidates for the treatment of obesity and diabetes. The new study shows how GIP lowers body weight. GIP is a hormone that is produced by the digestive tract. After eating, GIP stimulates the release of insulin and thus lowers blood sugar levels. The hormone also affects the regulation of appetite. However, the mechanisms and organs by which GIP affects body weight are unknown. Until now it was unclear whether the GIP receptor should be activated or inhibited to reduce body weight and what role the brain plays in the effects of GIP. “The aim of our studies was to find out whether the GIP receptor in the brain plays a special role in the effect of GIP,” said first author Qian Zhang from the Institute for Diabetes and Obesity at the Helmholtz Center in Munich.

GIP lowers body weight through brain-mediated inhibition of food intake

The researchers were able to show that administration of GIP reduced body weight and food intake in wild-type mice, but not in mice that lack the GIP receptor in the central nervous system.

Does the hormone affect certain areas in the brain? To answer this question, the researchers studied the brain activity of mice with diet-related obesity after they were treated with GIP. “This showed increased neural activity in areas of the hypothalamus that are associated with appetite control,” said Professor Christian Wolfrum from ETH Zurich. The authors conclude that the central regulation of food intake via GIP also includes the activation of important neurons in the hypothalamus.

New targets for the development of drug treatments for obesity and type 2 diabetes

The new findings are also important for the development of drug treatments for obesity and type 2 diabetes. Researchers at Helmholtz Zentrum München and Indiana University have developed a new therapeutic approach for type 2 diabetes. They combined hormones in a single molecule that work equally on the receptors of the insulin-stimulating hormones GLP-1 and GIP. The double agonist lowers body weight and improves blood sugar levels1. GLP-1 / GIP double agonists are already in phase 3 clinical trials. Clinical studies showed that GLP-1 / GIP reduced body weight more than treatment with GLP-1 alone.

However, these marked differences in weight loss were not observed in mice without a GIP receptor in the CNS, says Dr. Timo Müller, last author of the new study and acting director of the Institute for Diabetes and Obesity. Here the GLP-1 / GIP double agonist and the administration of GLP-1 reduce body weight equally. “Our research shows for the first time that the GLP-1 / GIP double agonist needs the GIP receptor in the brain in order to reduce body weight and food intake,” said DZD researcher Dr. Müller. “These results could help develop new drug targets that improve signal transmission and effectiveness of the GIP receptor. This could help to further increase the metabolic benefits of treatment with GIP and GLP-1 / GIP.”

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More information:
Qian Zhang et al., The glucose-dependent insulinotropic polypeptide (GIP) regulates body weight and food intake via the CNS GIPR signal Cell Metabolism (2021). DOI: 10.1016 / j.cmet.2021.01.015

Provided by the German Center for Diabetes Research DZD

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