August 02, 2006
Genetic Study Finds Hunger Enhancing Mutations

Better understanding of genetic mutations that cause obesity have led to identification of a compound that may reduce hunger in the obese.

Gainesville, Fla. -- Nearly 6 percent of morbidly obese children and adults have a genetic defect that keeps them feeling like their stomach is running on empty, no matter how much they have eaten.

The press release refers to genetic defects. The term "defect" implies an error or mistake. But a type of mutation that occurs in 6% of the population (correction: oops, 6% of the morbidly obese - gotta read more carefully) surely occurs at too high a frequency to be a mistake. The ancestors of the carriers of these mutations gained selective advantage and left more surviving offspring due to the mutations that made them more hungry.

The problem humans face today is that in industrialized countries mutations which increase the desire for food are now more a burden than a benefit. But the mutations are only defects if you use modern conditions as a reference to come up with standards for how humans should function.

Once you cross the bridge of defining modern civilization as the standard by which to decide which genetic variations are defects you've crossed a much larger bridge than most people appreciate. Consider the fight-or-flight reflex where someone feels adrenaline flowing and feels the urge to either run or attack. Since this reflex gets triggered totally inappropriately in arguments in office building meetings (few will start beating up co-workers or running for their lives down aisles of cubicles) it is hard to see the fight-or-flight reflex as adaptive at this point. If anything, the stress from adrenaline rush probably accelerates your aging.

If the fight-or-flight response and other counter-productive responses we have in modern situations are defects because they are counter-productive in modern conditions then all humans are full of defects and humanity is in need of a genetic redesign. I happen to think that, yes, we are in need of a massive redesign to adapt us to the technological and urban environments which we live in and to make it easier for us to live longer. But that will not become the majority view until we develop a far more detailed understanding of many genetic variations and how they govern the way we function.

These University of Florida scientists identified 11 mutations that make a receptor involved in hunger regulation to behave in ways that they consider to be abnormal.

Mutations of the melanocortin-4 receptor, a gene found in brain cells that play a role in regulating hunger, are the most common cause of genetic obesity. Now University of Florida researchers have determined how some of these mutations cause the receptor to miss signals from molecules that tell the body when to eat and when to put down the fork, placing scientists one step closer to finding a way to correct these defects.

In a side-by-side comparison of 40 genetic mutations, UF medicinal chemists found that 11 caused the receptor to behave abnormally, according to findings recently published in the online edition of the journal Biochemistry.

The goal is to discover the molecular glitch that causes the receptor to malfunction so chemists can make drugs to treat it, said Carrie Haskell-Luevano, Ph.D., a UF associate professor of medicinal chemistry and the study's lead author. UF researchers have already found a molecule that seems to correct one of the mutations, keeping the hunger-signaling pathway running smoothly, Haskell-Luevano said.

The collection of melanocortin-4 receptor gene mutations for obesity has been building up for years. See these papers from 1999 and 2004 for examples of earlier work on obesity and the melanocortin-4 receptor.

The discovery of more genetic variations that influence some behavior or metabolic processs opens up targets for drug development and also makes it easy to study the causes of differences in behaviors and metabolic processes.

Share |      Randall Parker, 2006 August 02 05:51 PM  Brain Appetite

Tom said at August 2, 2006 7:16 PM:

Randall: Re-read the quote - 6% of the morbidly obese is not 6% of the population.

This article: put the percentage of Americans that are morbidly obese at 2.2% in 2000, so we're talking about 6% of 2.2%, or 0.132%, or 1 in 757. That's in the ballpark with Down syndrome.

Randall Parker said at August 2, 2006 7:37 PM:


Oops. I stand corrected. I wonder if that percentage is high enough to be due to natural selection.

Tom said at August 3, 2006 3:25 AM:

Randall: If there was a single, consistant point mutation that caused this, I'd say yes. One mutation shouldn't happen that often. But this quote makes me think otherwise:

"In a side-by-side comparison of 40 genetic mutations, UF medicinal chemists found that 11 caused the receptor to behave abnormally, according to findings recently published in the online edition of the journal Biochemistry."

If a quarter of observed mutations on the gene cause it to behave oddly (and there are likely a lot more than 40 base pairs!), then it sounds like there are a ton of mutations on this gene that would cause it to act oddly. It could be that there's a reason that natural selection "wants" this diversity (like sickle cell), but absent any evidence of that, it seems more likely that this is just a genetically complicated (and thus fragile) receptor.

tanya medina said at August 3, 2006 4:01 PM:

Fat people just do not eat vegetables, skinny people generally eat salads fruits, and rarely grow their own grains to eat. People all over the world have gardens, fruit trees, and eat locally grown foods. the missing enzymes get destroyed by processed foods.
these obese people are ignoring common sense.
they need to buy a hydroponic garden and only eat what they sow, not everything that is convienent and easy. it is a mental illness, to over eat, binge eat everything in sight. I believe the pathogens and parasites take control of their hosts bodies to make those obese people addicted to their own pH and fermentation levels.

your jaw would get to tired to eat that many calories directly from the sun in the form of greens, and fruits.
Here is the culprit , it is the grains. I am thinking the chlorophyll is the antiaging and the starches are the feeder of the critters inside our guts. I just read this week that the virus that causes AIDS hides in the gut. So it makes sense to have an evacuated gut , so your body can rest and more readily fight of pathogens.
Only feed on dark greens (at least 70% of diet), then there is little sugars to feed the yeasts and bacterias , which help the virus and other gross things we dont even know about proliferate.
Think like making beer. certain grains have flavor , others provide body, and others will not turn into sugars without the help of enzymes. Beer also needs the hops to kill off what you dont want. (and you thought it was only for flavor)

I feel if there is a genetic single, consistant point mutation , it will be due to constant grain intake. perhaps like when they used to burn witches for eating the poison grains which made folks "trip out", perhaps timelines in our American revolution of fat people can be blamed on a few years of a grain virus? Perhaps due to genetically modified food crops?
here is a question for you, Is that gene they found in 6 % of the morbidly obese have in common , a precurser to Autism?
And what is the current percentage of morbidly obese individuals over the age of 90? How to lifecare facilities deal with this growing trend?

Bob Badour said at August 4, 2006 8:19 AM:

What I get out of this article is as many as 94% of the morbidly obese got that way without a defect in appetite. I don't think appetite is the problem per se. Insulin control is.

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