Team identifies weight-gain receptor linked to antipsychotic drugs

August 15, 2017, UT Southwestern Medical Center
UT Southwestern researchers (l-r) Drs. Joel Elmquist, Chen Liu, Syann Lee, and Caleb Lord. Credit: UT Southwestern

Many schizophrenic and depressed patients experience weight gain and type 2 diabetes in their quests for the life-changing benefits of a major class of antipsychotic drugs.

UT Southwestern Medical Center researchers identified a central to these undesirable effects. They then eliminated most of these metabolic changes in mice co-treated with a weight-loss drug that targets the 2c receptor.

"Atypical antipsychotics are essential medications for millions of schizophrenia patients worldwide and they are increasingly being prescribed for bipolar disorder, major depressive disorder, and autism," said Dr. Chen Liu, an Assistant Professor of Internal Medicine and Neuroscience and co-corresponding author of today's Journal of Clinical Investigation study along with Dr. Joel Elmquist, Director of the Division of Hypothalamic Research and a Professor of Internal Medicine, Pharmacology, and Psychiatry.

"Most members of this class of antipsychotics are linked to a drug-induced metabolic syndrome characterized by excessive , blood fat abnormalities, and type 2 diabetes. Obesity and diabetes often develop shortly after treatment begins," added Dr. Liu, who is also in the Division of Hypothalamic Research.

The researchers found that six weeks of exposure to the antipsychotic drug olanzapine caused weight gain - particularly in female mice - due to increased fat rather than muscle.

"Similar to treatment in humans, mice given olanzapine showed significant weight gain, higher food intake, and associated with insulin resistance and diabetes," said Dr. Caleb Lord, lead author of the study and a former postdoctoral researcher in the Division of Hypothalamic Research.

Next, they studied mice genetically modified to lack the serotonin 2c receptor. In those mice, the increased blood sugar and weight gain were almost absent, indicating that the serotonin 2c receptor must be present for olanzapine to cause , Dr. Liu said.

"Our study directly demonstrates in a mouse model that this interaction with the serotonin 2c receptor is a major cause of olanzapine's metabolic side effects. This finding is clinically significant because of an FDA-approved weight loss drug called lorcaserin, which in contrast to olanzapine, activates the serotonin 2c receptor. Based on the opposite effects of lorcaserin and olanzapine on the serotonin 2c receptor, we wanted to test whether lorcaserin treatment could counteract the metabolic effects of olanzapine. Co-treating with lorcaserin prevented weight gain and significantly improved the metabolic profile of mice treated with olanzapine," he said.

The researchers also found evidence that other mechanisms may be involved. Although the antipsychotic's usual effects on food intake, weight gain, and blood sugar were significantly blunted in mice lacking the serotonin 2c receptor, physical activity and energy expenditure remained lower despite the lack of that receptor. That finding indicates the involvement of other , the researchers said.

"This study suggests that by preventing the interaction between and the serotonin 2c receptor we might be able to eliminate many of the metabolic side effects without interfering with the psychiatric effects. We plan to continue working to understand the mechanisms involved," Dr. Liu said.

Explore further: The metabolic effects of antipsychotic drugs

Related Stories

The metabolic effects of antipsychotic drugs

July 12, 2011
Research to be presented at the upcoming annual meeting of the Society for the Study of Ingestive Behavior (SSIB), the foremost society for research into all aspects of eating and drinking behavior, may explain why some antipsychotic ...

Antipsychotics induce insulin resistance without weight gain

July 18, 2013
(HealthDay)—Atypical antipsychotic drugs induce insulin resistance even in the absence of weight gain and mechanisms regulating eating behavior, according to a study published online July 8 in Diabetes.

Tamoxifen protects against obesity-related metabolic disorders

May 11, 2017
Tamoxifen, a selective estrogen receptor modulator, is the gold standard for endocrine treatment of estrogen-receptor positive breast cancer. Tamoxifen is also known to have metabolic effects. A new study in The American ...

Study suggests that medication could improve gastric bypass results

July 8, 2015
New findings about the mechanisms involved - or not involved - in the effects of the most common form of bariatric surgery suggest that combining surgery with a specific type of medication could augment the benefits of the ...

Cannabinoids may be responsible for weight gain associated with schizophrenia

February 5, 2015
Cannabinoids may be involved in the weight gain that occurs in people with schizophrenia who are treated with the antipsychotic olanzapine, according to a pilot study published in the Journal of Clinical Psychopharmacology ...

Recommended for you

Exercise-induced hormone irisin triggers bone remodeling in mice

December 13, 2018
Exercise has been touted to build bone mass, but exactly how it actually accomplishes this is a matter of debate. Now, researchers show that an exercise-induced hormone activates cells that are critical for bone remodeling ...

Law professor suggests a way to validate and integrate deep learning medical systems

December 13, 2018
University of Michigan professor W. Nicholson Price, who also has affiliations with Harvard Law School and the University of Copenhagen Faculty of Law, suggests in a Focus piece published in Science Translational Medicine, ...

Drug targets for Ebola, Dengue, and Zika viruses found in lab study

December 13, 2018
No drugs are currently available to treat Ebola, Dengue, or Zika viruses, which infect millions of people every year and result in severe illness, birth defects, and even death. New research from the Gladstone Institutes ...

Faster test for Ebola shows promising results in field trials

December 13, 2018
A team of researchers with members from the U.S., Senegal and Guinea, in cooperation with Becton, Dickinson and Company (BD), has developed a faster test for the Ebola virus than those currently in use. In their paper published ...

Pain: Perception and motor impulses arise in brain independently of one another

December 13, 2018
Pain is a negative sensation that we want to get rid of as soon as possible. In order to protect our bodies, we react by withdrawing the hand from heat, for example. This action is usually understood as the consequence of ...

Researchers give new insight to muscular dystrophy patients

December 13, 2018
New research by University of Minnesota scientists has revealed the three-dimensional structure of the DUX4 protein, which is responsible for the disease, facioscapulohumeral muscular dystrophy (FSHD). Unlike the majority ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.