Summary: Researchers report a weight loss dampens the response to food cues in areas of the brain associated with emotion and attention.
Source: Beth Israel Deaconess Medical Center.
Results suggests drug could particularly benefit ’emotional eaters’.
A weight-loss drug dampened the response to food cues in regions of the brain associated with attention and emotion, leading to decreases in caloric intake, weight and body mass index (BMI), a team led by scientists at Beth Israel Deaconess Medical Center (BIDMC) reported. In the first study of the drug lorcaserin in the human brain, the research revealed the mechanism underlying the drug’s efficacy and provides insight into which individuals may benefit most from the medication. The paper was published today in the journal Diabetes, the journal of the American Diabetes Association.
“Human feeding behaviors involve areas of the brain responsible for cognitive control and decision-making,” said Christos S. Mantzoros, MD, Director of the Human Nutrition Unit in the Division of Endocrinology, Diabetes and Metabolism at BIDMC and Professor of Medicine at Harvard Medical School. “We wanted to find out if lorcaserin was acting on these brain regions and, if so, where and how. One-third of the U.S. population is obese, and another one-third is overweight. This is a huge burden on individuals and the health care system. In addition, it increases the risk of diabetes, cardiovascular disease and many types of cancer. We need to continue to develop safe and effective therapies to combat this epidemic.”
Approved by the FDA in 2012, the generic drug lorcaserin is a medication prescribed for obese or overweight adults who also have weight-related health complications such as diabetes. Several studies have shown the drug helps about half of the people who take it lose more than 5 percent of their body mass within a year, but there’s a great deal of variability in individual results, and the mechanism underlying its effect was previously unknown.
To determine how the drug works in the human brain, Mantzoros and colleagues observed 48 obese men and women – half taking the drug, half taking a placebo – over the course of a four-week experiment. Participants came into the clinic on four occasions for blood work, physical exams, measurements and weight-loss counseling with a registered dietician. They were also expected to keep records of the food they ate during the study.
On three visits – before receiving any medication (Week 0), after a week of medication (Week 1), and after four weeks of medication (Week 4) – exams were followed by two brain scans: one after the patients had fasted for at least 12 hours, the other after they had eaten a meal. The scans were taken using functional magnetic resonance imaging (fMRI) to measure changes in blood flow in an active brain, which suggests which regions play a role during a given task. During each scan, participants were shown 150 images of foods generally considered highly desirable, such as cake and onion rings; foods generally considered less desirable like vegetables; and nonfood items like rocks and trees.
At Week 1, the fMRI scans in the fasting state revealed that people taking the drug showed decreased brain activity in response to images of highly desirable foods in the attention-related parietal and visual cortices. At Week 4, the lorcaserin group in the fed state showed less activity in the parietal cortex – which is responsible for integrating sensory information – when looking at any of the food images.
The data also revealed that subjects who had the strongest brain responses to food prior to taking lorcaserin saw the most success with the weight-loss medication.
“Decreases in caloric intake, weight, and BMI were linked to strong responses to food cues in the areas of the brain related to emotion, pleasure and attention prior to taking the weight-loss drug, which suggests that lorcaserin could prove to be of particular benefit to ’emotional eaters,’ ” Mantzoros said.
Lorcaserin targets only a very specific serotonin receptor (known as 5-HT2c), shown in animal studies to play a role in abnormal food consumption. A previous generation of weight loss drugs was linked to this receptor, but because their scope was broader, those products also had dire cardiac side effects including pulmonary hypertension and valve problems. Lorcaserin could produce weight loss without these cardiac risks, the authors noted.
“In addition, the different mechanism of action in comparison to other drugs for obesity creates an opportunity for combination drugs for the treatment of obesity,” Mantzoros said. “This might create more powerful solutions and is something that remains to be explored.”
Funding: This work was funded by Harvard Clinical and Translational Science Center Grant (UL1 RR025758) from the National Center for Research Resources. Eisai, Inc. supported the study through an Investigator-Initiated Study grant. Eisai approved the design of the study, but had no role in study design; conduct of the study; collection, management, analysis, and interpretation of the data; or the preparation, review, or approval of the manuscript. Locaserin and placebo were provided by Arena Pharmaceuticals GmbH through Eisai, Inc. This study is also supported in part by the National Institutes of Health (DK081913). Olivia M. Farr was supported by fellowship grant 5T32HD052961.
Source: Jacqueline Mitchell – Beth Israel Deaconess Medical Center
Image Source: This NeuroscienceNews.com image is for illustrative purposes only.
Original Research: Abstract for “Lorcaserin administration decreases activation of brain centers in response to food cues and these emotion- and salience-related changes correlate with weight loss effects: a four week long randomized, placebo-controlled, double-blinded clinical trial” by Olivia M. Farr, Jagriti Upadhyay, Anna Gavrieli, Michelle Camp, Nikolaos Spyrou, Harper Kaye, Hannah Mathew, Maria Vamvini, Anastasia Koniaris, Holly Kilim, Alexandra Srnka, Alexandra Migdal, and Christos S. Mantzoros in Diabetes. Published online September 2016 doi:10.2337/db16-0635
[cbtabs][cbtab title=”MLA”]Beth Israel Deaconess Medical Center . “Study Reveals Weight Loss Drug’s Effect on Brain.” NeuroscienceNews. NeuroscienceNews, 12 September 2016.
<https://neurosciencenews.com/emotional-eater-brain-5023/>.[/cbtab][cbtab title=”APA”]Beth Israel Deaconess Medical Center . (2016, September 12). Study Reveals Weight Loss Drug’s Effect on Brain. NeuroscienceNews. Retrieved September 12, 2016 from https://neurosciencenews.com/emotional-eater-brain-5023/[/cbtab][cbtab title=”Chicago”]Beth Israel Deaconess Medical Center . “Study Reveals Weight Loss Drug’s Effect on Brain.” https://neurosciencenews.com/emotional-eater-brain-5023/ (accessed September 12, 2016).[/cbtab][/cbtabs]
Abstract
Lorcaserin administration decreases activation of brain centers in response to food cues and these emotion- and salience-related changes correlate with weight loss effects: a four week long randomized, placebo-controlled, double-blinded clinical trial
Lorcaserin is a serotonin 5HT-2c receptor agonist effective in treating obesity. While studies in rodents have shown that lorcaserin acts in the brain to exert its weight reducing effects, this has not yet been studied in humans. We performed a randomized, placebo-controlled, double-blind trial with 48 obese participants to study the effects of lorcaserin on the brain using functional magnetic resonance imaging (fMRI). Subjects taking lorcaserin had decreased brain activations in the attention-related parietal and visual cortices in response to highly palatable food cues at 1 week in the fasting state and in the parietal cortex in response to any food cues at 4 weeks in the fed state. Decreases in emotion and salience-related limbic activity, including the insula and amygdala, were attenuated at 4 weeks. Decreases in caloric intake, weight, and BMI correlated with activations in amygdala, parietal and visual cortices at baseline. These data suggest that lorcaserin exerts its weight reducing effects by decreasing attention-related brain activations to food cues (parietal and visual cortices), as well as emotional/limbic activity (insula, amygdala). Results indicating that baseline activation of the amygdala relates to increased efficacy suggest that lorcaserin would be of particular benefit to emotional eaters.
Previous use of serotonergic agonists, such as fenfluramine, are linked to non-selective activation of 5-HT2 receptors that led to various cardiac problems. However, since a 5-HT2c receptor antagonist blocked the weight reducing effects of fenfluramine, the more selective activation of 5-HT2c receptors by lorcaserin would produce this anti-obesity benefit seemingly without cardiac risk. Knock-out mice for the 5-HT2c receptors show higher body weight as a result of abnormal food consumption, further confirming the role of this receptor in obesity. These animals exhibit changes in metabolic hormones, developing insulin and leptin resistance and moreover impaired glucose tolerance, in addition to prolonged meal duration and frequency. A similar mechanism may contribute to the significant improvement in the levels of fasting serum glucose, total cholesterol, triglycerides and blood pressure seen in patients treated with lorcaserin.
“Lorcaserin administration decreases activation of brain centers in response to food cues and these emotion- and salience-related changes correlate with weight loss effects: a four week long randomized, placebo-controlled, double-blinded clinical trial” by Olivia M. Farr, Jagriti Upadhyay, Anna Gavrieli, Michelle Camp, Nikolaos Spyrou, Harper Kaye, Hannah Mathew, Maria Vamvini, Anastasia Koniaris, Holly Kilim, Alexandra Srnka, Alexandra Migdal, and Christos S. Mantzoros in Diabetes. Published online September 2016 doi:10.2337/db16-0635
