August 12, 2006
Hypothalamus Chemical Key To Appetite Control

Gene therapy to deliver a gene to break down malonyl CoA boosts appetite in rats.

In their latest finding on the brain's role in controlling appetite and weight, researchers at the Albert Einstein College of Medicine have shown that reducing levels of fatty acids in the hypothalamus causes rats to overeat and become obese. Their results suggest that restoring fatty-acid levels in the brain may be a promising way to treat obesity. The study, published in the January 15th on-line edition of Nature Neuroscience, was led by Dr. Luciano Rossetti, director of the Diabetes Research Center at Einstein. (The paper will appear in print in the February issue.)

Consumption of fats causes a boost in malonyl CoA in the hypothalamus. Reduction in malonyl CoA boosts appetite.

The study focused on malonyl CoA, a molecule suspected of being one of the critical nutrients influencing hypothalamic regulation of eating behavior. Previous studies had shown that hypothalamic levels of malonyl CoA increase markedly after meals and are suppressed by fasting.

The Einstein researchers wanted to know whether sustained suppression of this nutrient within the hypothalamus could result in obesity. To find out, they piggybacked an enzyme known to degrade malonyl CoA onto an adeno-associated virus and injected the virus into the hypothalamus of rats. The injections caused a chronic decrease in malonyl CoA levels, which dramatically increased the rats' food intake and led to obesity that was maintained for at least four months.

"We showed in this study that disrupting malonyl-CoA levels in this region of the brain impairs the nutrient-sensing mechanism by which the hypothalamus modulates food intake to maintain normal weight," says Dr. Rossetti, who is also the Judy R. and Alfred A. Rosenberg Professor of Diabetes Research at Einstein. "Figuring out a way to re-adjust malonyl-CoA levels in the human hypothalamus could lead to innovative therapies not only to treat obesity but to help prevent diabetes and other consequences of being overweight."

If drugs can be found that either boost malonyl CoA levels in the hypothalamus such drugs might decrease appetite. Alternatively, malonyl CoA binds somewhere to cause the appetite suppression effect. Another option is to look for where it binds and develop drugs that bind at the same place. A malonyl CoA substitute migh also suppress appetite.

Another possibility: Would slow consumption of small amounts of a fat all day reduce total calories consumed? If so, would all fats work equally well for this purpose? Or do particular fats do a better job of suppressing appetite? If so, which fats best suppress appetite?

Share |      Randall Parker, 2006 August 12 11:13 AM  Brain Appetite


Comments
Bob Badour said at August 12, 2006 5:53 PM:
If drugs can be found that either boost malonyl CoA levels in the hypothalamus such drugs might decrease appetite.

As you speculate later in your post, such a drug already exists: fatty acids.

The dietary recommendations to get most calories from carbohydrates and to avoid fatty foods are insane for fat people. A better diet plan is to focus on getting enough micronutrients, fiber, protein and fat while avoiding unecessary carbohydrates. If one is getting enough micronutrients and fiber from one's diet, one will get plenty of carbohydrates. The fiber and fats will suppress appetite.

One will probably have to supplement with potassium, though, to avoid muscle cramps and to keep the heart operating optimally unless one has a rich source of potassium in the diet too.

Which fatty acids? If one eats animal protein, one will get most of their fat that way. Avoiding bioaccumulated toxicity and improving omega 3/6 ratios seem prudent for those fat sources. For plant fats, I suspect the best are tocotrienol+tocopherol-rich saturated and mono-unsaturated plant fats, and one should adjust these up or down depending on how much fat one gets from animal protein sources.

Mary said at March 8, 2007 3:44 PM:

I'm wondering if taking the supplement Omega 369 would help. Have any studies been done on this?

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