Johns Hopkins brain scientists have hit on how and why some powerful drugs used for treating mental illnesses cause patients to gain so much weight that they often develop life-threatening complications such as diabetes and heart disease. “We’ve now connected a whole class of antipsychotics to natural brain chemicals that trigger appetite,” says Solomon H. Snyder, M.D., professor of neuroscience at the Johns Hopkins School of Medicine. “Our identification of the molecular players that link such drugs to increased food intake means there’s now hope for finding a newer generation of drugs without the weight-gain side effects.”
.Previous research already had fingered increased levels and actions of one particular enzyme, AMPK, in brain cells as a control lever for appetite in mice and presumably humans.
Suspecting that antipsychotic drugs might spike AMPK in the brain to overact, the Johns Hopkins team injected mice with clozapine (Clozaril), which, with olanzapine (Zyprexa) and risperidone (Risperdal), is commonly prescribed for schizophrenia and bipolar disorder in people who do poorly on conventional drugs.
Mice given clozapine showed quadrupled AMPK activity compared to activity measured pre-drug. The researchers then gave the mice leptin, a hormone that suppresses appetite, and as suspected, saw lowered AMPK levels.
Drilling down further into what controls AMPK and its boost of hunger, Sangwon Kim, Ph.D., a research associate and lead author of the study, “rounded up the usual suspects, brain proteins known to relay communication from cell to cell.”
Systematically manipulating these cell-signaling proteins, Snyder’s team found that blocking one in particular, a receptor site for histamine, a well-known player in triggering classic allergy symptoms, activates AMPK to the same extent as clozapine. To confirm that the histamine receptor connects the drug, AMPK activity and appetite, the team gave clozapine to mice genetically engineered without a histamine receptor. Results? No heightened AMPK activity.
“Histamine also has a long history as a suspect in weight control, but no one ever could put a finger on the exact link,” says Snyder. “The connection we’ve made between its receptor and appetite control is incredibly intriguing and opens new avenues for research on weight control, possibly including drugs that suppress appetite safely.”
Authors on the paper are Kim, Alex Huang, Adele Snowman and Snyder of Hopkins, and Cory Teuscher of the University of Vermont College of Medicine. Published Feb. 20th online at the Proceedings of the National Academy of Sciences. http://neuroscience.jhu.edu/index.php
More Reasons You Should NOT Rely on Bottled Water: German researchers have found that the longer a bottle of water sits on a store shelf or in a household pantry, the higher the dose of antimony it contains. Amounts of this potentially toxic trace element were measured for 15 brands of Canadian bottled water and 48 European brands. Concentrations reached more than 100 times the average level of antimony in pristine groundwaters (2 parts per trillion). However, the concentration was even higher after the bottles were left to sit at room temperature for six months. Antimony concentrations in the Canadian bottled waters increased by 19 percent, concentrations in the European brands increased by 90 percent. Most of the water tested was packaged in bottles made of polyethylene terephthalate (PET). Antimony trioxide is used as a catalyst in the manufacture of PET. The different concentrations of antimony in the various brands might have been caused by differing temperatures, water pHs, or exposure to sunlight.