Eat more, move less and don’t gain weight by blocking a marijuana-like chemical in the brain

Unless you're a rodent, it's probably too early to get excited about the possibility of being able to eat all you want, be a couch potato and still not gain weight, but new research using a strain of specially-modified mice indicates that just such an unlikely scenario might one day be possible. Recently, a team of scientists from UC Irvine (UCI), Yale and Marche Polytechnic University in Ancona, Italy discovered they could bring this metabolic miracle about in the lab by blocking the actions of a marijuana-like compound that regulates energy metabolism.

To bring about this hypermetabolic state, the researchers, led by UCI pharmacology professor Daniele Piomelli, altered forebrain neurons in mice to reduce production of a substance called 2-Arachidonoylglycerol (2-AG). Evidently, all mammalian brains contain 2-AG, a naturally-produced endocannabinoid compound. The team believes this plays a role in regulating the forebrain neural circuits that take part in energy dispersal.

When these 2-AG-deprived mice were observed, they consumed more food and were more sedentary than their unmodified cousins but gained no extra weight, even when fed high-fat chow. Especially interesting was the absence of any signs of the symptoms collectively known as metabolic syndrome, such as high blood pressure and elevated blood sugar - conditions that can eventually lead to heart disease and obesity.

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

So what, exactly, was going on? Mammals have two types of adipose (fat) tissue: white and brown. The white stores calories while the brown burns them for energy and heat production. In the mice with reduced 2-AG, their brown fat became hyperactive and began converting into heat at a greatly accelerated rate compared to normal mice. That's information that could potentially turn the multi-billion dollar weight-loss industry on its head.

Obviously, we can't go around modifying human brains to produce less 2-AG in an effort to create a race of lazy, svelte gluttons, but could some kind of weight-gain prevention drug based on this data one day find its way into the pharmaceutical pipeline?

"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," Piomelli cautioned. "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."

The team's study appears in the March 2012 issue of the journal Cell Metabolism.

Source: UC Irvine

More about endocannabinoids

Endocannabinoids are compounds naturally produced in our bodies that activate cannabinoid receptors. In an odd twist of science, researchers discovered the first cannabinoid receptor back in 1988, years before they discovered its activating molecule. It wasn't until 1992 that the first receptor ligand, arachidonoylethanolamine or AEA (dubbed Anandamide after the Sanskrit word for bliss, ananda) was identified. Although its molecular structure is different, it has properties similar to tetrahydrocannabinol or THC, the psychoactive ingredient in marijuana (also known as cannabis sativa/indica).

Endocannabinoids modulate a number of factors in the human body, including pain, mood and appetite, so there's currently a flurry of drug research in this area, especially with regard to cannabis, which contains at least 85 different cannabinoids. Interestingly, cannabis, when consumed raw (not heated or dried) is not psychoactive, which has led to a budding (pun intended) subculture of devotees who eat or juice the raw leaves for their numerous medical benefits.