Genetic Link to Alcoholism and Obesity: A New Study in Molecular Psychiatry

[selfAdjoint]

Are you a persistent drunk? Have you not seen your toes since you were a kid? You like to blame it on your genes, right? Now see this (new paper in the wonderfully titled journal Molecular Psychiatry - only the abstract is free, but that should suffice.

http://www.nature.com/mp/journal/v11/n9/abs/4001856a.html

 

[Gelsamel Epsilon]

Wow that's awesome, the genetic front is really pushing on and ahead into greater things.

 

[chroot]

Obesity used to be a rare disease, but has risen so rapidly that it affects nearly half the US population -- after only a couple of generations. Is obesity heritable? Give me a break.

- Warren

 

[Bystander]

PC genetics --- nothing is anyone's fault. Strange twist on Cotton Mather's (?) "Sinners in the hands of an angry god" determinism.

 

[selfAdjoint]

Obesity used to be a rare disease, but has risen so rapidly that it affects nearly half the US population -- after only a couple of generations. Is obesity heritable? Give me a break.

- Warren

"I refuse to look at this experimental evidence because
a) I know better, and
b) I have an oversimplified argument which attacks a straw man version not present in the paper."

Give ME a break!

 

[chroot]

If you don't eat it, it can't end up on your thighs. It's the conservation of mass, selfAdjoint. Regardless of any proof of genetic predisposition towards, say, food addiction, virtually all fat people are fat because they eat too much. Period. There really cannot be much debate about this.

- Warren

 

[Rade]

If you don't eat it, it can't end up on your thighs. It's the conservation of mass, selfAdjoint. Regardless of any proof of genetic predisposition towards, say, food addiction, virtually all fat people are fat because they eat too much. Period. There really cannot be much debate about this.

With all due respect to your status on PF--there is widespead evidence of genetic desposition to obesity--I provide a few reports below. As stated in link #3 below, obesity is not a simple lack of free will responsibility--but a very complex disease that now effects vast numbers of humans:
http://hmg.oxfordjournals.org/cgi/content/abstract/ddl204v1
http://www.ncbi.nlm.nih.gov/entrez/...ve&db=PubMed&list_uids=11087657&dopt=Abstract
http://www.muhealth.org/weightlosssurgery/understanding.shtml
http://query.nytimes.com/gst/fullpage.html?sec=health&res=9904EFDB173FF93BA25757C0A9609C8B63

 

[Gelsamel Epsilon]

But what drives those people to eat more and more? If they're eating because they're depressed, then why choosing eating, and not say - cutting - when depressed?

 

[selfAdjoint]

If you don't eat it, it can't end up on your thighs. It's the conservation of mass, selfAdjoint. Regardless of any proof of genetic predisposition towards, say, food addiction, virtually all fat people are fat because they eat too much. Period. There really cannot be much debate about this.

- Warren

My family tends to run to weight. When I was married my weight hovered just above 270, and my wife was fat too. Was it because we ate too much? You betcha! And I drank too much also. My two children also tend to put it on, and the tendency has descended to my eldest grandaughter. Too much eating? Yes indeed!

But since I've been a widower I've lost 100 lbs; my weight now hovers just above 170 and my BMI is between 21 and 22. Eating less? That's how I did it.

But a while back I was talking to my kids and I mentioned that I almost never feel hungry, or full. When I read about tricks for "satisfying your appetite" with low calorie food, I am bemused, because as far as I've ever been able to tell, I have no appetite. I don't eat to feel less hungry, I eat for mouth sensations; taste texture and so-on. And I have lost that weight by exploiting this trait; I eat very little mass and drink a lot of fluids. Mostly water.

And when I said these things to my kids they responded: "That's the way we are too!" Does this lack of a clear signal from our digestion maybe have a bearing on our weight problems? Could be. And if so, might there be a connection to dopamine processing in the brain? Not unthinkable. And if THAT is so, could there be a genetic reason for it? Yup.

"Make everything as simple as possible, but not more simple than possible".

 

[Rade]

But what drives those people to eat more and more? If they're eating because they're depressed, then why choosing eating, and not say - cutting - when depressed?

They are not eating more and more--they are eating less and less of proper molecules in balance. See the third link provided above--the genetics for obesity has always been present for > 50,000 years in humans--excessive fatty molecules in modern diet act as trigger to activate genes that allow fatty tissue to accumulate out of proposition to the mass eaten. Now add on lack of exercise (e.g., too many folks typing on PF ) and here we are--modern day epidemic. Good news--if genetic based--then genetic cure possible.

 

[chroot]

With all due respect to your status on PF--there is widespead evidence of genetic desposition to obesity--I provide a few reports below. As stated in link #3 below, obesity is not a simple lack of free will responsibility--but a very complex disease that now effects vast numbers of humans:

Do you dispute my statement that, if you do not eat it, it cannot end up on your thighs?

Do you dispute my statement that the vast majority of fat people would lose weight if they simply began expending more calories than they consume?

In this western world, we're in an age of almost universal literacy, universal nutrition labels, easy access to healthy foods in well-stocked supermarkets, and cheap food scales. There is absolutely no excuse for anyone to "accidentally" eat 300 lbs more food than they need. If people claim their bodies cannot self-regulate via normal hunger and satiety stimuli, then they can buy a damn food scale, or read the nutrition labels, and use their brains instead. This is assuredly NOT rocket science, and we don't need any deep genetic studies showing us how it's "okay" to be porkers. Obesity is not a disease of the genes, it's a disease of the fork.

- Warren

 

[Mickey]

I think it's pretty obvious that biology determines how much you like alcohol. Some people from all sorts of environments just don't need or want it. Observations of primates that trespass on public beaches and steal people's drinks also show that the same proportion of them prefer alcohol as the human population.

Whether there is a recognizable biology for the abuse of alcohol is sketchy. Obviously, the more you like it, the more likely you are to abuse it, but that's hardly a determining factor. Some people who don't like it still abuse it, likely as a means of fitting in.

If you don't eat it, it can't end up on your thighs. It's the conservation of mass, selfAdjoint. Regardless of any proof of genetic predisposition towards, say, food addiction, virtually all fat people are fat because they eat too much. Period. There really cannot be much debate about this.

Well, you're right, regarding the fact that good scientific answers are ultimately not debatable, but biological systems do not treat mass equally, the way a physicist does. Your body does not treat all mass the same, nor does your body treat certain kinds of mass the same as another person's body might. Just because obesity is correlated with mass doesn't mean it's physics.

You've probably seen people eat ridiculous amounts of food, not do any exercise, and remain thin as a rod. That's because they were born with an ectomorphic biology. Such people are annoyed when you marvel at how thin they are. It's not something that's up to them, and they'd probably rather have a more muscular and mesomorphic body.

Anyway, I don't think genes are the biggest problem in the obesity epidemic. It's a hugely subsidized sugar industry, creating an evolutionary shocking surplus of cheap refined sugar products. This affects lower income people more, because they naturally want to maximize the amount of energy they receive per dollar spent. Homo sapiens evolved in an environment where sugar was not as plentiful, so we adapted mechanisms to store it. These mechanisms have gradually become unnecessary. However, subsidizing the sugar industry accelerated this change and created a hostile environment, which people are still trying to adapt to.

Instead of wasting time and energy adapting to a hostile environment, we should just remove the subsidies, so that we can spend more time and energy adapting to natural changes.

 

[selfAdjoint]

As Lubos Motte found out, you cannot explain a change by something that predicts a constant level, so any hereditary component of the propensity to gain weight can't be blamed for a new epidemic of obesity. That doesn't mean such a hereditary component doesn't exist, and indeed it has been shown to exist.

 

[Rade]

Do you dispute my statement that, if you do not eat it, it cannot end up on your thighs?

Yes. You can eat 0 % fat yet still have fat end up on your thighs--has to do with carbohydrate metabolism

Do you dispute my statement that the vast majority of fat people would lose weight if they simply began expending more calories than they consume?

No--but they could still be obese. There is a difference between being overweight and being obese. In fact, one can be obese yet not overweight, or overweight but not obese. Thus an obese person with genetic disposition can expend more calories, become less overweight, yet still maintain physiological state of obesity due to genetic inability to metabolize fat molecules.

 

[chroot]

Yes. You can eat 0 % fat yet still have fat end up on your thighs--has to do with carbohydrate metabolism

I mentioned nothing about fat versus carbohydrates, nor is it relevant. A person who is 100 lbs overweight has eaten a minimum of 100 lbs more food, over their lifetime, than needed. There can be no argument about this.

No--but they could still be obese. There is a difference between being overweight and being obese. In fact, one can be obese yet not overweight, or overweight but not obese. Thus an obese person with genetic disposition can expend more calories, become less overweight, yet still maintain physiological state of obesity due to genetic inability to metabolize fat molecules.

You're saying the definition of "obesity" is a genetic one? You understand, I hope, that your definition disagrees with that of every dictionary in print.

- Warren

 

[Gelsamel Epsilon]

I think it's more saying that disposition towards eating, metabolism rate, and other factors which could be gene-determined increase the expression of the obesity phenotype. This is not to say that obesity is not affected by environmental stimulus. Genetics 101 really. You can't really disagree with that.

But as chroot said, in the end it is upto the person in question making a conscious decision to eat the food and not burn it.

 

[hypatia]

When you are born, you have every fat cell in place. You gain no more fat cells in your life. The amount and placement of these cells is determened by genes. Thats why you see big bottoms and thighs on some, or big bellies on others.
It is now pretty clear that obesity is not just a matter of excess weight, because fat cells do not merely store fat: They send out bioactive molecules with powerful effects throughout the body. If you have more fat cells, its easier to gain weight, and harder to loose it.

So the statement "It really is in your genes!" is very correct. But we also know, it can be over come with lifestyle changes. You may just half to work a bit harder at it.

 

[chroot]

If you have more fat cells, its easier to gain weight, and harder to loose it.

If a person needs 2,000 calories for their basal metabolism, yet eats only 1,500 calories per day, they have a deficit of 500 calories per day. This translates to a weight loss of one pound of pure fat per week.

I see no reason why "having more fat cells" could possibly invalidate this simple fact. Can you please explain how "having more fat cells" can allow one to escape the conservation of mass?

I believe your "having more fat cells" mumbo-jumbo is just more fat-sympathizing propaganda, to help people marginalize personal accountability for weight. "It doesn't matter what I eat, I can't lose weight! You see, I'm above the fundamental laws of physics, because I have more fat cells!"

- Warren

 

[Bystander]

When you are born, you have every fat cell in place. (snip)

Hardly --- cells don't increase in size as we grow, they increase in number --- feed the fat, they increase --- feed the lean, they increase.

 

[chroot]

Hardly --- cells don't increase in size as we grow, they increase in number --- feed the fat, they increase --- feed the lean, they increase.

Actually, hypatia is correct about this -- fat cells really do grow and shrink as they store and release fat.

Hypatia's just incorrect in saying that somehow the absolute number of fat cells in one's body makes losing weight more or less difficult. That's just pandering, and cannot be physically valid.

- Warren

 

[Bystander]

Guess I'll have to throw a slice of bacon under a microscope some time. Still strikes me as a bit odd that a couple pounds of baby fat can turn into a couple hundred pounds of health hazard without some increase in number of cells.

 

[selfAdjoint]

Chroot, I don't disagree with your reductionism on the subject of pounds and calories, but I do object to your hectoring tone and pejorative vocabulary ("pandering" , etc.).

I've been fat and I'm now thin; I have seen the inside (for me) of both states, and this finger-pointing, as if every attempt to understand the subtleties of human nutrition was just some scheme to let those disgusting, guilty, stupid fat people off the hook just (ahem) turns my stomach. Do you carrry on like this in your professional activities?

 

[hypatia]

Fat cells send messages to the brain about the body's nutrient levels, and these signals create the urge to eat. One of the signaling hormones is leptin, which is made by fat cells. High leptin levels discourage individuals from eating. Conversely, people who cannot produce leptin are constantly obsessed with food, always hungry, and grotesquely obese. These individuals can be treated directly with leptin.

Keep in mind, treatment with leptin does not work for most obese individuals. That's because they can make leptin - and actually have elevated levels of the hormone compared to people that are not obese - but environmental and genetic factors have raised the amount of leptin required to make individuals feel full. When body fat falls, so do leptin levels, sparking intense cravings for food and overeating. Which makes it much more of a struggle to loose weight.
Other hormones involved in regulating appetite include appetite-increasing ghrelin, made by empty stomachs, and the appetite-suppressing cholecystokinin and peptide YY, produced by the intestines when the stomach is full. There is quite a lot of research being done in these areas.

A good diet and exercise, eating less and burning more will work for everyone. I would never say other wise,you miss-understood me Warren. All I have said is that its more of a struggle when your body is sending you "eat more" message.

 

[chroot]

hypatia,

I have only experienced a single life, and my views are colored by the fact that I do not seem to suffer from any sort of addictive personality traits. Most of your arguments boil down to the fact that fat people are fat because their bodies give their brains incorrect hunger and satiety stimuli, and they respond accordingly.

My argument boils down to the notion that people are sentient, capable of reason and arithmetic, and should have higher-level control over their behavior, well beyond the simple stimulus-response model.

I can empathize with a characteristically obese person with some kind of hormonal problem leading to a constant feeling of hunger. I can understand that it's probably a very uncomfortable situation. I cannot understand how such a person cannot find another way of managing the condition besides simply giving in and becoming obese.

And, despite the lament of fat people everywhere, most studies indicate that the vast majority of fat people are fat simply because they eat too much, and not because they suffer from some endocrine disorder. We're approaching the 1-in-3 mark for clinical obesity in this country. I don't believe for an instant that 30% of the US population mysteriously suffers from an endocrine disorder. After all, the problem seems to much more prevalent in the US than outside, and it even seems correlated among subpopulations, like Houston. This all points to a behavioral problem, not a genetic one.

selfAdjoint,

I did not use the words "disgusting," "guilty," or "stupid," so I must conclude that they represent your own latent feelings, and you simply wish to project them on me. I certainly do not intend to dehumanize fat people, or call them names. I simply think that fat people need to accept responsibility for their own actions, and not hide behind tired excuses like "I have more fat cells." If fat people simply wish to be fat, let them accept both the responsibility and the consequences. They have a choice, and they have chosen poorly. So be it.

I, for one, am just tired of the "feel good about being fat" memes that now seem to saturate American culture. I'm tired of people re-labeling themselves "big beautiful women" and telling others to feel good about their poor lifestyle choices. I'm tired of restaurants offering bovine-sized portions marketed as "hungry man" entrees.

- Warren

 

[selfAdjoint]

No I am not projecting; I was attributing to you what I inferred form your anumus in these exchanges. But from you response to Hypatia I have changed my opinion. Not ever having been subjected to the feelings or level of temptations that others are, you assume that they should have no more trouble kicking the habit than you do in avoiding it. You assume everybody is "rational" above all and have a moral parti pris for that state of psychology. But it's not a realistic belief, Chroot. My own experience is that I couldn't lose weight until I got control of my own household and could ensure that the fattening things that taste so good to me weren't around. My "reason" has to sub for my "will power". I of course am only one voice, but everybody has a story.

 

[Curious3141]

Chroot, while I agree with your obvious point that weight gain can only be due to an excess of caloric intake, you seem to be missing the large glaring point about basic human drives and discomfort. People differ not just in how their body "handles" the food (metabolism), they also differ in how their brain perceives the adequacy of their intake (satiety). Hunger is a powerful drive, and there are few things more uncomfortable and distracting than to go hungry for more than half the day.

If you truly believe you are a completely "rational" person and able to command yourself to function normally despite what your nervous/humoral system is nagging your consciousness about, then let's put it to the test. I will gladly volunteer to pay my own way to the US if you'll agree to let me shadow you for a full month while jabbing a big sharp (but sterilised) safety pin in your buttocks during half your waking hours. Let's see if you can work/live with any semblance of normality with that constant intrusive nociceptive input to your brain.

Try that, and you may get an idea of how difficult it is for people who're genetically predisposed to crave more food to live normally while denying themselves.

If you can't meet my challenge, perhaps you should drop the insensitive, self-righteous tone.

 

[chroot]

Curious3141,

Despite not having the "endocrine disorder" that suddenly seems to affect more than a third of the US population, I actually have experienced hunger before. And no, hunger is not the perceptual equivalent of being repeatedly stabbed with a needle, at least not until it reaches the point where malnourishment begins to threaten life. I'm pretty sure that the vast majority of the fat people in Houston are not suffering from crippling malnourishment.

What I keep repeating over and over again in this thread is that the vast majority of fat people do not have some crippling endocrine disability that makes them feel so hungry they can't even function without a half-gallon of Ben & Jerry's every day. Most fat people are fat because they choose to eat too much, not because of malfunctioning sateity stimulus. Quit repeating that tired line about satiety! If you don't believe me, look at the literature. Most fat people are not hungry!

Most fat people are fat because they give into marketing, don't understand portion sizes, don't pay attention to calories, choose foods poorly, don't exercise, use food to cope with environmental stress, and choose to selectively forget about the 800 kcal worth of "light snacks" they consume everyday. There are myriad psychological, social and economic reasons why our culture is mostly overweight these days, but something like 95% of fat people have perfectly-functioning biological "machinery."

Virtually all fat people who proclaim that they can't help being fat (because of genes, etc.) are simply trying to avoid taking responsibility for themselves.

- Warren

 

[Curious3141]

Curious3141,

Despite not having the "endocrine disorder" that suddenly seems to affect more than a third of the US population, I actually have experienced hunger before.

And what leads you to believe that any hunger you've experienced is of the same severity or of the same compelling nature as an overweight person on a diet? It's like me (a guy) saying a difficult childbirth is no big deal, we've all experienced "pain" before.

And no, hunger is not the perceptual equivalent of being repeatedly stabbed with a needle

Of course it isn't. You seem to have missed the point that it was an analogy. Not having experienced the same hunger that many obese people report, you are really in no position to make comparisons between the severity of being poked by a needle and someone else's hunger (that really was my whole point).

Lest you turn that around on me, I will state now that I *am* obese, and have been so for many years. And I have tried and failed to lose weight by dieting. Believe me, the hunger can be very, very bad, and there were times when I wished it was a needle being jabbed in my flesh rather than the interminable hunger pangs.

What I keep repeating over and over again in this thread is that the vast majority of fat people do not have some crippling endocrine disability that makes them feel so hungry they can't even function without a half-gallon of Ben & Jerry's every day. Most fat people are fat because they choose to eat too much, not because of malfunctioning sateity stimulus. Quit repeating that tired line about satiety! If you don't believe me, look at the literature. Most fat people are not hungry!

Right, let's look at the literature, shall we? Right off the bat : http://www.ncbi.nlm.nih.gov/entrez/..._uids=16815794&query_hl=3&itool=pubmed_docsum

I don't have the full text, but quoting from the abstract,

Considerable attention is currently being paid to the secular changes in food intake and physical activity that underlie the increase in the prevalence of obesity that is apparent in many societies. While this is laudable it would be unwise to view these environmental factors in isolation from the biological factors that normally control body weight and composition and the compelling evidence that inter-individual differences in susceptibility to obesity have strong genetic determinants. This is particularly important, as it is only in the past decade that we have begun to obtain substantive information regarding the molecular constituents of pathways controlling mammalian energy balance and therefore, for the first time, are in a position to achieve a better mechanistic understanding of this disease. Population-based association and linkage studies have highlighted a number of loci at which genetic variation is associated with obesity and related phenotypes and the identification and characterization of monogenic obesity syndromes has been particularly fruitful. While there is widespread acceptance that hereditary factors might predispose to human obesity, it is frequently assumed that such factors would influence metabolic rate or the selective partitioning of excess calories into fat. However, it is notable that, thus far, all monogenic defects causing human obesity actually disrupt hypothalamic pathways and have a profound effect on satiety and food intake. To conclude, the evidence we have to date suggests that the major impact of genes on human obesity is just as likely (or perhaps more likely) to directly impact on hunger, satiety and food intake rather than metabolic rate or nutrient partitioning. At the risk of oversimplification, it seems that from an aetiological/genetic standpoint, human obesity appears less a metabolic than a neuro-behavioural disease.

Now you rebut that with your own examples from the literature.

Most fat people are fat because they give into marketing, don't understand portion sizes, don't pay attention to calories, choose foods poorly, don't exercise, use food to cope with environmental stress, and choose to selectively forget about the 800 kcal worth of "light snacks" they consume everyday. There are myriad psychological, social and economic reasons why our culture is mostly overweight these days, but something like 95% of fat people have perfectly-functioning biological "machinery."

Virtually all fat people who proclaim that they can't help being fat (because of genes, etc.) are simply trying to avoid taking responsibility for themselves.

- Warren

I'm glad you feel that you're such an expert on the behavior of a group of people you've admittedly never belonged to, and never studied rigorously either. Tell me, how much of your bold declaration can honestly be considered scientifically defensible, and how much simply belongs to the realm of "prejudiced tirade" ?

 

[chroot]

And what leads you to believe that any hunger you've experienced is of the same severity or of the same compelling nature as an overweight person on a diet? It's like me (a guy) saying a difficult childbirth is no big deal, we've all experienced "pain" before.

Not having actually had a person poking you in the posterior with a needle for half your waking hours, you are really in no position to make comparisons between the severity of being poked by a needle and your own hunger.

...Do you really not see your own hypocrisy?

Lest you turn that around on me, I will state now that I *am* obese, and have been so for many years. And I have tried and failed to lose weight by dieting.

Obviously, the physical fact is that, even while dieting, you continued to eat just as many calories as before, and that's why dieting didn't work. You probably believe many of the same rationalizations that other fat people choose to believe: I'm fat, and there's nothing at all I can do about it. Dieting just doesn't help!

Your adherence to those kinds of comforting falsehoods explains your aggressive posturing, too. You have fought long and hard to distance yourself from any personal accountability for your own weight. Here's a hint: hire a nutritionist full-time to monitor and record all your food intake for a week or two. Or end up bedridden and have a doctor put you on a gastric bypass diet. Guess what? You'll lose weight incredibly quickly. Your weight problem is not your body's fault.

Now you rebut that with your own examples from the literature.

Happily.

http://www.ncbi.nlm.nih.gov/entrez/...uids=16210723&query_hl=21&itool=pubmed_docsum

CONCLUSIONS: Our data suggest that the familial resemblance in physical activity in these children is explained predominantly by shared environmental factors and not by genetic variability.

http://www.cdc.gov/nccdphp/dnpa/obesity/contributing_factors.htm#Genetics

However genes do not always predict future health. Genes and behavior may both be needed for a person to be overweight. In some cases multiple genes may increase one’s susceptibility for obesity and require outside factors; such as abundant food supply or little physical activity.

In other words, eating too much and exercising too little are the dominant reasons why fat people are fat. Sure, there may be some genetic predisposition to obesity, just like there is for alcoholism. On the other hand, your genes don't actually make you fat. Your eating and exercise habits are the cause. You just need to learn to accept that.

Alcoholism has a very similar disease profile to chronic obesity, yet acoholics are generally willing to acknowledge that nothing more than their own actions are what led to their condition. Sure, they may have a genetic predisposition, and that may lend them some comfort, but very few are content to just throw up their hands, kill themselves with alcohol, and say "I can't help being an alcoholic! It's in my genes!"

I'm glad you feel that you're such an expert on the behavior of a group of people you've admittedly never belonged to, and never studied rigorously either. Tell me, how much of your bold declaration can honestly be considered scientifically defensible, and how much simply belongs to the realm of "prejudiced tirade" ?

Despite that fact that so many hurt feelings and sensitive social issues are wrapped up in our obesity epidemic, it does not chance the scientific facts. I am being truly impartial here -- I am simply repeating the unequivocal, honest truth: most fat people are fat because they allow themselves to be fat. Your desperate need to defer accountability for your own actions is not relevant to me.

- Warren

 

[chroot]

And Curious3141, I can't help but be curious...

Can you tell us exactly how many calories you consume each day? Can you tell us about your exercise schedule?

- Warren