Opioid receptors as a drug target for stopping obesity

ScienceDaily (July 31, 2012) — New research demonstrates that blocking the delta opioid receptor in mice created resistance to weight gain and stimulated gene expression promoting non-shivering thermogenesis.

See Also:Health & MedicineDiet and Weight LossObesityFitnessMind & BrainDieting and Weight ControlOpiumNutrition ResearchLiving WellReferenceDetox dietSouth Beach dietCalorie restricted dietAdipose tissue

Imagine eating all of the sugar and fat that you want without gaining a pound. Thanks to new research published in The FASEB Journal, the day may come when this is not too far from reality. That's because researchers from the United States and Europe have found that blocking one of three opioid receptors in your body could turn your penchant for sweets and fried treats into a weight loss strategy that actually works. By blocking the delta opioid receptor, or DOR, mice reduced their body weight despite being fed a diet high in fat and sugar. The scientists believe that the deletion of the DOR gene in mice stimulated the expression of other genes in brown adipose tissue that promoted thermogenesis.

"Our study provided further evidence that opioid receptors can control the metabolic response to diets high in fat and sugar, and raise the possibility that these gene products (or their respective pathways) can be targeted specifically to treat excess weight and obesity," said Traci A. Czyzyk, Ph.D., a researcher involved in the work from the Department of Physiology at the Mayo Clinic in Scottsdale, Arizona.

Scientists studied mice lacking the delta opioid receptor (DOR KO) and wild type (WT) control mice who were fed an energy dense diet (HED), high in fat and sugar, for three months. They found that DOR KO mice had a lean phenotype specifically when they were fed the HED. While WT mice gained significant weight and fat mass on this diet, DOR KO mice remained lean even though they consumed more food. Researchers then sought to determine how DOR might regulate energy balance and found that DOR KO mice were able to maintain their energy expenditure levels, in part, due to an increase in non-shivering thermogenesis. This was evidenced by an increase in thermogenesis-promoting genes in brown adipose tissue, an increase in body surface temperature near major brown adipose tissue depots, and the ability of DOR KO mice to maintain higher core body temperatures in response to being in a cold environment.

"Don't reach for the ice cream and doughnuts just yet," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. "We don't know how all this works in humans, and of course, a diet of junk food causes other health problems. This exciting research identifies genes that activate brown adipose tissue to increase our burning of calories from any source. It may lead to a safe diet pill in the future."

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FDA unveils safety measures for opioid painkillers

Drugmakers that market powerful painkiller medications will be required to fund training programs to help U.S. doctors and other health professionals safely prescribe the drugs, which are blamed for thousands of fatal overdoses each year.

The safety plan released by the Food and Drug Administration on Monday is designed to reduce misuse and abuse of long-acting opioid pain relievers, which include forms of morphine, methadone and oxycodone. The agency's plan mainly involves educating doctors and patients about appropriate use of the drugs.

The FDA has issued a number of warnings on prescription pain relievers in recent years but with little effect. Inappropriate use of the drugs caused nearly 425,000 emergency department visits in 2009, according to government figures. The drugs were blamed for 15,600 deaths that year, up from 14,800 in 2008.

The FDA said companies that sell the drugs must offer two to three hours of training to prescribers, either for free or for a small fee. The courses will be designed by companies that provide continuing medical education for health professionals, not by the drugmakers themselves.

The agency wants companies to provide training to least 60 percent of the 320,000 U.S. prescribers of the drugs within three years of launching the programs. The programs, which will be vetted by FDA regulators, must be available by March 2013.

"Responsible physicians will welcome the education benefits provided by this program," said Dr. Lynn Webster of the American Academy of Pain Medicine.

In addition to training, drugmakers will be required to distribute safety brochures to patients explaining the risks of the drugs and instructions to seek emergency care in event of an overdose.

The FDA spent more than three years developing the so-called risk management plans for the drugs, with input from industry and health care professionals.

Some health care experts stressed that training should be required for all prescribers. But FDA officials said the programs will be optional for now because making them mandatory would require a new law by Congress.

The new FDA plan covers about 30 opioid drugs, including Purdue Pharma's OxyContin, Johnson & Johnson's Duragesic patch and Pfizer's Embeda. Opioids are drugs that simulate the effects of natural narcotics, such as the opium poppy. They are typically prescribed for people already taking pain medications, including cancer patients, to treat severe pain flare-ups.

The products targeted by the FDA feature extended-release formulations designed to give long-lasting effects. But that potency carries serious risks when doctors prescribe them inappropriately, and when patients abuse them as stimulants.

The FDA reports that many physicians prescribe the painkillers for patients with migraine headaches, an unapproved use. Patients will also sometimes chew extended-release pills that are designed to be swallowed, causing an overdose.

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