Overview: Triptans, a commonly prescribed drug for migraine relief, may be effective in treating obesity. Daily triptan exposure led to reduced food intake and increased weight loss in mouse models.
sauce: UT Southwestern
Triptans, a commonly prescribed class of migraine medications, may also help treat obesity, a new study by UT Southwestern scientists suggests.
In a study of obese mice, the team reported that daily doses of triptans caused animals to eat less and lose weight during the month. Experimental Medicine Journal..
“We have shown the real potential to reuse these drugs already known to be safe for appetite suppression and weight loss,” said Internal Medicine and Neuroscience. Dr. Chen Liu, an assistant professor and research leader, said. Researcher at Peter O’Donnell Jr. Brain Institute.
Obesity affects more than 41% of all adults in the United States and increases the risk of heart disease, stroke, diabetes, and certain types of cancer. Most treatments for obesity focus on diet and physical activity.
Scientists have long known that serotonin, a chemical messenger found throughout the brain and body, plays an important role in appetite. However, there are 15 serotonin receptors. It is a molecule that senses serotonin and signals cells to change their behavior accordingly.
Researchers have a hard time understanding the role of each serotonin receptor in appetite, and previous drugs such as fenphen and lorcaserin (Belvic) targeting specific individual receptors are on the market due to side effects. Withdrew from.
Triptans used to treat acute migraine and cluster headaches target serotonin 1B receptors (Htr1b), another receptor that has not been well studied in the context of appetite and weight loss. It works.
For a new study, researchers tested six prescription triptans in obese mice fed a high-fat diet for seven weeks. Mice given two of these drugs ate about the same amount, while mice given the other four ate less.
After 24 days, mice receiving a daily dose of frovatriptan lost an average of 3.6% of body weight, whereas mice not receiving a triptan gained an average of 5.1% of body weight. .. Dr. Liu and his colleagues saw similar results when transplanting a device that gives a stable dose of frovatriptan to animals for 24 days.
“We have found that these drugs, especially one, can lose weight and improve glucose metabolism in less than a month, which is very impressive,” said Dr. Liu.
Since triptans are commonly prescribed for short-term use during migraine headaches, Dr. Liu suspects that patients may not have noticed long-term effects on appetite and weight in the past.
To accurately determine how frovatriptan affects food intake and body weight, researchers lack either Htr1b or Htr2c, which are serotonin receptors targeted by fenphen and lorcaserin. I designed the mouse so that. In mice without Htr1b, frovatriptan was unable to reduce appetite or cause weight loss, but excision of Htr2c had no effect. This confirms that the drug works by targeting the serotonin 1B receptor.
“This discovery can be important for drug development,” said Dr. Liu. “We not only shed light on the possibility of reusing existing triptans, but also focused on Htr1b as a candidate for treating obesity and regulating food intake.”
The team also showed exactly which neurons in the brain were most important for the role of Htr1b in mediating appetite, homing to a small group of cells in the hypothalamus of the brain.
Other researchers who have 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 from UT Southwestern. Ohjin Oh and Jong-Woo Sohn of the Korea Institute of Science and Technology; Lin Jia of the University of Texas at Dallas; Guanlin Wang of the University of Oxford; Catherine Nautiyar of the University of Dartmas. René Hen of Columbia University.
Funds: This study was funded by the National Institutes of Health (R01 DK114036, DK130892, F32DK116427, K01AA024809), the American Health Association (16SDG27260001), the UTSW Pilot and Feasibility Award, and the Outstanding Grossman Foundation Award for Diabetes Research.
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About this neuropharmacology and weight loss research news
author: Press office
sauce: UT Southwestern
contact: Press Office – UT Southwestern
image: The image is in the public domain
Independent research: Closed access.
Chen Liuetal. “Depiction of Serotonin 1B Receptor Circuit for Appetite Suppression in Mice” by. Experimental Medicine Journal
Overview
Depiction of serotonin 1B receptor circuit for appetite suppression in mice
Triptans are a commonly prescribed anti-migraine drug. Here we report their previously unrecognized role in suppressing the appetite of mice. In particular, frovatriptan treatment reduces food intake and body weight in diet-induced obese mice.
In addition, the appetite-suppressing effect depends on serotonin (5-HT) 1B receptors (Htr1b).By ablation Htr1b In four different brain regions, Htr1b Engage in spatiotemporally isolated neural pathways to regulate postnatal growth and food intake.
moreover, Htr1b AgRP neurons in the arcuate nucleus (ARH) of the hypothalamus contribute to the appetite-reducing effect of HTR1B agonists. To further study the appetite-suppressing Htr1b circuit, Htr1b-Cre mouse.
You will find that ARH Htr1b Neurons regulate food intake bidirectionally in vivo.In addition, mononuclear RNA-Seqing analysis revealed that: Htr1b Marks a subset of AgRP neurons. Finally, we used a cross-sectional approach to specifically target these neurons (Htr1b).AgRP Neuron)..
Shows that they partially regulate food intake via Htr1bAgRP→ PVH circuit.
