May 17, 2006
Amino Acid Leucine Reduces Appetite In Rats

Eating more leucine might help reduce appetite to make it easier to lose weight.

CINCINNATI--A cell-signaling pathway in the brain that is linked to the development of cancer and diabetes is also a key part of networks that regulate food intake, say University of Cincinnati (UC) researchers.

The finding might one day lead to new ways of helping obese people lose weight, either with new drugs or by carefully designing diets that can activate this pathway.

Scientists from UC's Genome Research Institute demonstrated that the signaling pathway mTOR--activated by nutrient and hormonal signals--plays a role in the brain's ability to sense how much energy the body has available.

As more biochemical pathways by which appetite gets regulated become identified and understood in greater detail they become obvious targets for appetite suppressing drug development.

This finding, the researchers say, suggests that very specific micronutrients may drive these pathways in the brain and could lead to a more scientific approach to diet design to help regulate body weight.

The study, led by Randy Seeley, PhD, professor in UC's psychiatry department, appears in the May 12, 2006 issue of the journal Science.

One caveat: These researchers used rats, not humans.

Another caveat: The method of leucine delivery was injection, not diet. They injected it into a specific area of the brain no less. So that's a big caveat. Will it produce the same effect when consumed?

The mTOR pathway is very sensitive to "branched-chain" amino acids, particularly leucine, Dr. Seeley explains. In laboratory studies, he and his team found that when they administered leucine directly to the hypothalamus, a brain region that controls a number of metabolic processes, animals ate less.

Other, similar amino acids did not give the same results.

This animal study, says Dr. Seeley, could eventually have implications for human obesity.

"Rather than basing our diets only on macronutrients like fat or carbohydrates, we might one day be designing diets based on micronutrients like amino acids," he says.

The amount of food consumed dropped by a sixth.

To see whether the mTOR pathway in the hypothalamus responds to amino acids, Seeley injected 1 microgram of leucine directly into the brains of rodents, near the hypothalamus. Over the next day, the rats that received the injection consumed 25 grams of food on average while the control rats consumed 30 g of food.

A reduction in calories consumed by a sixth per day would prevent weight gain in most people. It would also allow for a slow weight loss.

They saw an even larger reduction in calories consumed when leucine was delivered after a 24 hour fast. But to do 24 hour fasts would probably require a far more effective appetite suppressant. If we had such a powerful appetite suppressant we wouldn't need leucine.

You can buy L-Leucine as a powder or capsule. The powder form would be cheaper. I'm not encouraging anyone to try this. Also, if you do try it I would suggest you do so in moderation. Amino acids compete with each other for absorption in a few transport mechanisms that bring amino acids into cells. You don't want to starve your cells of other amino acids by saturating one of those transport mechanisms. Though I'm not sure that's a real problem.

A Yale online survey found people very willing to take risks to lose weight.

New Haven, Conn. - Nearly half of the people responding to an online survey about obesity said they would give up a year of their life rather than be fat, according to a study by the Rudd Center for Food Policy and Obesity at Yale.

The 4,000 respondents in varying numbers between 15% and 30% also said they would rather walk away from their marriage, give up the possibility of having children, be depressed, or become alcoholic rather than be obese. Five percent and four percent, respectively, said they would rather lose a limb or be blind than be overweight.

"We were surprised by the sheer number of people who reported they would be willing to make major sacrifices to avoid being obese. It drives home the message that weight bias is powerful and pervasive," said Marlene Schwartz, associate director of the Rudd Center and lead author of the study in Obesity, which was issued this month.

15% would give up 10 years of life to be skinny.

15 percent said they would trim a decade off their lives for a thinner waistline.

Whatever company comes up with a really powerful yet safe appetite suppressant is going to make billions of dollars in profits. Mind you, such a treatment has to test as safe chiefly for the benefit of regulatory agencies. Many of the potential customers are willing to run bigger risks.

Share |      Randall Parker, 2006 May 17 10:01 PM  Brain Appetite

Joe said at May 18, 2006 5:41 AM:

"15 percent said they would trim a decade off their lives for a thinner waistline"

The funny thing is that they could lose weight and live 10 years LONGER. People make it sound like it is impossible to lose weight. I lost 40 lbs in 1 year by making very minor changes to my diet. I guess people just want the easy way out.

hamerhokie said at May 18, 2006 7:20 AM:

Branched chain amino acids have been an expensive supplement in the fitness industry for some time now. Used by bodybuilders to cut fat, and to regulate protein synthesis post-workout.

Lou Pagnucco said at May 18, 2006 9:20 AM:

A cautionary note -

Reduced mTOR signaling may be one of the chief mechanisms responsible for the longevity increasing effect of
caloric restriction. Possibly, the weight loss from CR diets is not the central factor which lengthens life spans.

Since leucine increases mTOR signaling (and growth hormone synthesis), it could conceivably accelerate aging.

Legal lady said at May 18, 2006 12:04 PM:

People would gitve up a LIMB rather than be obese??? That is incredible. And another thing-the fact that people claim they would give up so much in order not to be fat, and yet they won't give up fatty foods or actually exercise doesn't make sense!

Dave said at May 19, 2006 8:24 AM:

That people would give up a limb to lose weight is understandable - in fact, those who have parts of their stomachs and intestines removed do exactly that.

The drive to consume calories is built in and - along with the appetite amping of the advertising world - the reduced time and labor available to actually shop and cook - and the strong revenue driven motive to increase restaurant portion sizes, the calorie winds blow in exactly the wrong direction. The desire to lose weight is simply not sustainably strong in most people to overcome the instantaneous reflex/response to immediate desire and "oh - one more won't hurt" rationalization. Self control is maddeningly hard. I cannot prove, but believe that in addition to being necessary, eating is a mild addiction - but an addiction nonetheless.

Bob Badour said at May 19, 2006 12:55 PM:


I reiterate your focus on appetite is misplaced. Metabolism is where the solution lies.

We have developed the means to produce an abundance of food we never evolved to use for energy. Rapeseed, corn and even wheat are relatively recent additions to our diet, and they now form a huge amount of the modern diet. The problem does not lie in appetite but in adapting to the diet we now have.

You focus on obesity while ignoring the other contemporary epidemic: malnutrition.

Reducing appetite will only reduce the vitamins and other micronutrients most people currently fail to consume enough of.

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