AUG 15, 2017 04:55 PM PDT

Understanding why Antipsychotic Drugs Cause Weight Gain

WRITTEN BY: Carmen Leitch
2 7 510

Weight gain is an unfortunate side effect of many antipsychotic drugs like olanzapine. It’s important to help patients manage these unwanted complications, especially to improve their quality of life but also because the weight gain comes with health problems. There is some good news on that front; researchers have identified a serotonin receptor that’s responsible for the weight gain that often accompanies these drugs. The work, performed by researchers at the University of Texas Southwestern Medical Center, was published in the Journal of Clinical Investigation and is outlined in the following video.

"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," commented Dr. Chen Liu, an Assistant Professor of Internal Medicine and Neuroscience.

"Most members of this class of antipsychotics are linked to a drug-induced metabolic syndrome characterized by excessive weight gain, blood fat abnormalities, and type 2 diabetes. Obesity and diabetes often develop shortly after treatment begins."

When the investigators exposed mice to the drug olanzapine over a period of six weeks, the drug caused the mice to gain weight. That weight gain was especially pronounced in female mice, who gained additional body fat.

"Similar to treatment in humans, mice given olanzapine showed significant weight gain, higher food intake, and metabolic changes associated with insulin resistance and diabetes," explained Dr. Caleb Lord, who worked as a postdoctoral researcher in the Division of Hypothalamic Research.

However, mice that were genetically modified so they would not have a serotonin 2c receptor did not exhibit weight gain after drug exposure, nor did they have an increase in blood sugar. That showed the receptor was important to the mechanism by which these drugs cause weight gain.

Weight gain is an unwanted side effect of antipsychotic drugs / Credit: Max Pixel

"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," Liu explained.

"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,” Liu continued.

The findings were encouraging. “Co-treating with lorcaserin prevented weight gain and significantly improved the metabolic profile of mice treated with olanzapine,” noted Liu.

While it remains to be seen whether these results will hold true for people, it is an important step toward relieving patients suffering from depression and schizophrenia of these side effects.

Other factors may also be at play as well, the researchers noted. While expected drug effects were reduced in the mice without the serotonin receptor, energy expenditure and physical activity was still low, and not ameliorated by the gene edit. The investigators noted that the suggests that other molecules or receptors are an influence.

“This study suggests that by preventing the interaction between antipsychotic drugs 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,” Liu concluded.

 

 

Sources: UPI Via University of Texas Southwestern Medical Center, JCI

About the Author
  • Experienced research scientist and technical expert with authorships on 28 peer-reviewed publications, traveler to over 60 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
JUN 12, 2018
Cancer
JUN 12, 2018
CD44 Insights & Cancer Influence
CD44 is a known cell surface protein involved in numerous interactions; it is overexpressed in cancerous tissue and its isoforms are being investigated as targets for cancer immunotherapy
JUN 16, 2018
Cell & Molecular Biology
JUN 16, 2018
Watching the Movement of Stem Cells
Video is changing the way data is collected in the lab.
JUN 20, 2018
Cell & Molecular Biology
JUN 20, 2018
Some Cells can Suppress Fat Formation
Scientists discovered a new kind of human cell that interferes with the creation of fat cells.
JUL 07, 2018
Genetics & Genomics
JUL 07, 2018
Cause of Gender Differences in Neurodevelopmental Disorders is ID'ed
Gender is a known factor in the development of neurological disorders. Now scientists think they know why.
JUL 09, 2018
Cell & Molecular Biology
JUL 09, 2018
Scientists Found a New Way to Treat Lung Cancer
Small cell lung cancer is an aggressive type that can be fatal; there were few treatments for the disease. That may have changed.
JUL 16, 2018
Cell & Molecular Biology
JUL 16, 2018
Preventing Aging by Protecting Ribosomes
We carry many genes for ribosomes in case we need backup copies - those parts of the genome tend to suffer damage.
Loading Comments...