Blocking natural, marijuana-like chemical in the brain boosts fat burning

Stop exercising, eat as much as you want ... and still lose weight? It sounds impossible, but UC Irvine and Italian researchers have found that by blocking a natural, marijuana-like chemical regulating energy metabolism, this can happen, at least in the lab.

To create this hypermetabolic state, UCI pharmacology professor Daniele Piomelli and colleagues engineered neurons in the forebrains of mice to limit production of an endocannabinoid compound called 2-AG. All mammalian brains contain 2-AG, which the researchers believe helps control the activity of forebrain involved in .

As a result, these modified mice ate more and moved less than typical mice but did not gain any weight, even when they were fed a high-fat diet. Additionally, they did not develop any signs of , a combination of health problems such as obesity and that increases the and diabetes.

"We discovered that these mice were resistant to obesity because they burned fat calories much more efficiently than normal mice do," said Piomelli, the Louise Turner Arnold Chair in the Neurosciences. "We had known that endocannabinoids play a critical role in cell , but this is the first time we found a target where this occurs."

Specifically, these stayed thin because their brown fat – a type of fat that exists in all mammals to keep them warm – became hyperactive and was converted into heat at a much more rapid pace than in ordinary mice.

Does this mean that a drug limiting 2-AG levels may one day become a weight-loss panacea? That's more easily said than done, according to Piomelli. For the study, the mice were bred with brain cells manipulated to limit 2-AG production – which can't be done with humans.

"To produce the desired effects, we would need to create a drug that blocks 2-AG production in the brain, something we're not yet able to do," he explained. "So don't cancel that gym membership just yet. But as you hit the treadmill, think about the added health benefits if you could train your brain to make fewer endocannabinoids."

Findings appear in the March issue of Cell Metabolism. Nicholas DiPatrizio, Giuseppe Astarita, Kwang-Mook Jung, Jason Clapper, Ana Guijarro, Dean Thongkham and Agnesa Avanesian of UCI; Giuseppe D'Agostino and Sabrina Diano of Yale University; and Andrea Frontini and Saverio Cinti of Marche Polytechnic University in Ancona, Italy, contributed to the study, which received support from the National Institute on Drug Abuse.

About endocannabinoids

Endocannabinoid compounds are created naturally in the body and share a similar chemical structure with THC, the primary psychoactive component of the marijuana plant, Cannabis. Endocannabinoids are distinctive because they link with protein molecule receptors – called cannabinoid receptors – on the surface of cells. For instance, when a person smokes marijuana, the cannabinoid THC activates these receptors. Because the body's natural cannabinoids control a variety of factors – such as pain, mood and appetite – they're attractive targets for drug discovery and development. Piomelli is one of the world's leading endocannabinoid researchers. His groundbreaking work is showing that this system can be exploited by new treatments to combat anxiety, pain, depression and obesity.

Provided by University of California - Irvine

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foolspoo
1 / 5 (1) Mar 06, 2012
scary... on all accounts
tadchem
not rated yet Mar 06, 2012
Piomelli and colleagues limited production of the endocannabinoid and the "modified mice ate more and moved less than typical mice but did not gain any weight, even when they were fed a high-fat diet." - That sounds eerily familiar. They got the munchies, but stayed skinny?
qitana
not rated yet Mar 06, 2012
There was a drug called Rimonabant, which worked in a similar way, probably as an inverse agonist for the cannabinoid system.

It was withdrawn from the market, it worked for obesity but it was a cause of severe depression and a risk for suicidal behaviour

Not to condemn it completely, but it doesn't look to be the best way to tackle obesity.
qitana
not rated yet Mar 06, 2012
Actually, I do condemn it completely, it is not responsible
gwrede
not rated yet Mar 06, 2012
To move less and eat more, bliss on Earth. This will become the defining drug for the next two decades. Unfortunately.
lisa7777
not rated yet Mar 06, 2012
Wow I have never heard anything like that before. I get all my weight loss tips and reviews from weightnatural.com
jscroft
not rated yet Mar 06, 2012
Then maybe you shouldn't get your weight-loss tips from a malware site. Jacka$$.
Jstashe
not rated yet Mar 07, 2012
This article is silly.

Blocking the effects of endocannabinoids for diet pills has already been done before.

A drug called Rimonobant.

It had to be removed from the market because the other major effects are severe depression and suicidal behavior.

Endocannabinoids are also neuroprotective and shield the CNS from damage in multiple ways.

In time, the CB1 and CB2 receptor systems will most likely also be known for feelings of well being.

Blocking endocannabinoids from properly functioning seems unwise.
antonima
not rated yet Mar 07, 2012
Yeah, what Jstashe said .. you will lose weight and eat more too if you expose yourself to cold temperatures or high stress. Shivering, cold sweat, and malaise may not be that good of an alternative to healthy exercise.

However, I suppose this depends on the individual, and how they cope with depression and exercise!