Summary: Triptans, drugs commonly prescribed for migraine relief, may be effective in treating obesity. Daily exposure to triptans reduced food intake and increased weight loss in mouse models.
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Triptans, a class of commonly prescribed migraine medications, may also be helpful in treating obesity, a new study by UT Southwestern scientists suggests.
In studies with obese mice, a daily dose of a triptan led the animals to eat less food and lose weight over the course of a month, the team reported in the Journal of Experimental Medicine.
“We have shown that there is real potential for repurposing these drugs, which are already known to be safe, for appetite suppression and weight loss,” said study leader Chen Liu, Ph.D., Assistant Professor of Internal Medicine and Neuroscience and researcher at the Peter O’Donnell Jr. Brain Institute.
Obesity affects more than 41% of all adults in the US and increases the risk of heart disease, stroke, diabetes, and certain types of cancer. Most obesity treatments focus on eating habits and physical activity.
Scientists have long known that serotonin, a chemical messenger found throughout the brain and body, plays a key role in appetite. However, there are 15 different serotonin receptors, molecules that detect serotonin and signal cells to change their behavior in response.
Researchers have struggled to understand the role of each serotonin receptor in appetite, and previous drugs, including fen-phen and lorcaserin (Belviq), that targeted certain individual receptors, have been withdrawn from the market due to side effects .
Triptans, which are used to treat acute migraines and cluster headaches, work by targeting a different receptor, serotonin receptor 1B (Htr1b), which had not been well studied before in the context of appetite and loss of appetite. weight, Dr. Liu said.
For the new study, the researchers tested six prescription triptans on obese mice that were fed a high-fat diet for seven weeks. Mice fed two of these drugs ate about the same amount, but mice fed the other four ate less.
After 24 days, mice given a daily dose of the drug frovatriptan lost an average of 3.6% of their body weight, while mice not given triptan gained an average of 5.1% of their body weight . Dr. Liu and his colleagues saw similar results when they implanted devices in the animals that gave them a constant dose of frovatriptan for 24 days.
“We found that these drugs, and one drug in particular, can reduce body weight and improve glucose metabolism in less than a month, which is quite impressive,” said Dr. Liu.
Since triptans are typically prescribed for short-term use during migraines, Dr. Liu suspects that long-term impacts on appetite and weight might not have been noticed by patients in the past.
To determine exactly how frovatriptan affects food intake and weight, the researchers engineered mice to lack Htr1b or Htr2c, the serotonin receptor targeted by fen-phen and lorcaserin. In Htr1b knockout mice, frovatriptan could no longer decrease appetite or cause weight loss, while Htr2c knockdown had no effect. This confirmed that the drug worked by targeting the serotonin 1B receptor.
“This finding could be important for drug development,” said Dr. Liu. “Not only do we shed light on the potential to repurpose existing triptans, but we also draw attention to Htr1b as a candidate for treating obesity and regulating food intake.”
The team went on to show exactly which neurons in the brain were most important to Htr1b’s role in mediating appetite, by targeting a small group of cells within the brain’s hypothalamus.
Other researchers who contributed to this study include Li Li, Steven C. Wyler, Luis A. León-Mercado, Baijie Xu, Swati, Xiameng Chen, Rong Wan, and Amanda G. Arnold of UT Southwestern; Youjin Oh and Jong-Woo Sohn of the Korea Advanced Institute of Science and Technology; Lin Jia of UT Dallas; Guanlin Wang of the University of Oxford; Katherine Nautiyal of Dartmouth College; and Rene Hen of Columbia University.
Money: The study was supported by the National Institutes of Health (R01 DK114036, DK130892, F32DK116427, K01AA024809), the American Health Association (16SDG27260001), a UTSW Pilot and Feasibility Award, and a Grossman Endowment Award for Excellence in Research. of diabetes.
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About this research news in neuropharmacology and weight loss
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Font: Southwest UT
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original research: Closed access.
“Delineation of a serotonin 1B receptor circuit for appetite suppression in miceby Chen Liu et al. Journal of Experimental Medicine
Summary
Delineation of a serotonin 1B receptor circuit for appetite suppression in mice
Triptans are a class of commonly prescribed migraine medications. Here, we report a previously unrecognized role for appetite suppression in mice. Notably, frovatriptan treatment reduced food intake and body weight in diet-induced obese mice.
In addition, the anorexigenic effect depends on the serotonin (5-HT) 1B receptor (Htr1b). ablation Htr1b in four different brain regions, we show that Htr1b participates in spatiotemporally segregated neuronal pathways to regulate postnatal growth and food intake.
It’s more, Htr1b in AgRP neurons in the arcuate nucleus of the hypothalamus (ARH) contributes to the hypophagic effects of HTR1B agonists. To further study the Htr1b anorexigenic circuit, we generated Htr1b-Cre mice.
We find that ARH Htr1b neurons bidirectionally regulate food intake in vivo. Furthermore, single core RNA sequencing analyzes revealed that Htr1b marks a subset of AgRP neurons. Finally, we used an intersectional approach to specifically target these neurons (Htr1bAgRP neurons).
We show that they regulate food intake, in part, through an Htr1bAgRP→PVH circuit.
