New Genes IDd in Obesity: How Much of Weight is Genetic?

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Two studies zero in on DNA-based drivers of weight. Is obesity written in our genes?

In two separate papers, published in the journal Science and in the Journal of Clinical Investigation (JCI), researchers describe new genetic factors that could explain weight gain in some people. In the Science study, researchers at Boston Children’s Hospital studying mice found a rare genetic mutation that prevented the animals from burning off fat calories. They also found the same gene was mutated in a group of obese people. And a team based at University College London reported in JCI that a specific form of a gene previously linked to obesity, FTO, can increase craving for high-fat foods.

The discoveries add to the growing body of knowledge about the biology behind weight, and the results confirm that while it’s represented by a single number, weight is the complex combination of a multitude of different metabolic processes, from brain systems that regulate appetite to enzymes that control how efficiently calories are turned from food into energy that the body needs. Making matters even more confusing, these factors are also likely influenced by environmental contributors such as diet and lifestyle.

In the mouse study, the research team determined that mutations in the Mrap2 gene led the animals to eat less initially but still gain about twice as much weight as they normally would. While their appetites returned, these mice continued to gain weight despite being fed the same number of calories as a group of control animals. That led the scientists to figure out that the mice with the mutated gene were simply sequestering fat rather than breaking it down for energy. The mice, like people, possessed two copies of the gene, and mice with even one defective copy experienced significant weight gain, although not as much as those who had two mutated versions of Mrap2.

The scientists found a similar pattern among a group of 500 obese people; they detected four mutations in the human version of Mrap2, and each of the obese individuals possessed only one bad version of the gene.

(MORE: Study Identifies Four New Genetic Markers For Severe Childhood Obesity)

In the British study, the researchers divided a group of 359 healthy men of normal weight by their FTO gene status. The majority of the men had low-risk versions of the gene, while 45 of the participants had mutations that have been linked to greater appetite and caloric consumption. To figure out how the altered genes were affecting appetite, the team measured levels of the hunger hormone ghrelin both before and after meals that the participants ate; the men with the mutated form of FTO did not show the same drop in ghrelin levels, signifying that they were full, as the men with the low-risk form of FTO.

Genome wide association studies, which compare genetic makeups of obese individuals to those of normal weight, are making it easier to flesh out important genetic factors contributing to weight, and researchers at the Harvard School of Public Health say that to date, these studies have identified over 30 candidate genes on 12 chromosomes associated with body mass index.

“Thus far mutations in about eight genes are known to cause obesity in humans. But these mutations account for under five percent of the obesity in our society, and certainly are not, by themselves, responsible for the current obesity epidemic, since the mutation rate in these genes could not have changed dramatically during the past twenty years,” says Dr. Joseph Majzoub, the chief of the division of endocrinology at Boston Children’s Hospital and an author on the Science paper. “However, mutations in these genes have led to the discovery of pathways that are important in energy balance in humans, giving us hope that drugs can be developed that affect these pathways to prevent excessive weight gain, either by curbing appetite or increased burning of calories.”

(MORE: What Mice Can Tell Us About Obesity and Genetics)

Here is a round-up of some recent genes, and their products, that have been linked to obesity :

Leptin: Often referred to as the “obesity hormone,” leptin is made by fat cells and acts as a thermostat for the body’s energy needs. Each individual has his own leptin threshold; if leptin levels fall below that amount, the brain understands that the body is starving, and needs more calories. If leptin levels are maintained or surge above that amount, the brain knows that it doesn’t need to take in more food. Unfortunately, while mouse studies showed that overweight mice had lower levels of leptin, the same wasn’t true of obese people, who generally show higher levels of leptin in their blood. Somehow, researchers how believe, these people are not getting the signal to stop eating, which is referred to as leptin-resistance.

Ghrelin: This gene makes an appetite hormone that can make foods look more desirable–especially high-calorie ones — by influencing the brain’s reward system. Some studies have found that  people who are sleep-deprived have increased ghrelin levels, which may explain why lack of sleep can contribute to weight gain.

Neuropeptide Y: One of the brain’s many chemicals, neuropeptide Y may trigger eating by manipulating appetite, possibly resulting from changes in mood and stress levels. It may also contribute to an increased deposition of fat from food calories.

(MORE: Childhood Obesity: Scientists Find Two Gene Variants that Predispose Kids to Weight Gain)

136 comments
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nomi

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nomi
nomi

certainly think its a little of both genetics and the environment affecting obesity.  Genetics also affects behavior and because of this alone we would say genetics and obesity are linked .. word to pdf

JenJenJen
JenJenJen

Just quick note. Bariatric surgeries like gastric sleeve or gastric bypass are proven to be highly successful in helping people lose weight. How do these surgeries work? By either making your stomach smaller or allow food to bypass your stomach - end result: you feel full faster and eat less; hence you lose weight. This proves that the major cause of obesity is what type of food a person chooses to eat and how much they eat. Genes may play a role in predisposing a person to obesity but that's not an excuses for obese people to say it's not their fault, otherwise these surgeries won't be so successful in making obese people lose weight.

So yeah... Stop eating high calorie foods like no other and control your mouth. Have willpower and say no to cravings. Then, you will lose weight or to the least extent won't get fatter.

JenniferIllsleyMilford
JenniferIllsleyMilford

I'm obese. At just 5'1", I weigh over 250. Here is the thing though. My diet was very controlled growing up. I ate the same way as my skinny sibling growing up. I was active growing up (except when my asthma got in the way, which was a result of genetics, not my weight problem). My mom was thin and my dad, while not thin was definitely under control. I never understood why I had such a hard time with my weight. Then I hit puberty early and by the time I was 12, I had a bra size that would make a porn star jealous but had gained the weight to match it. Around this time my great aunt moved to town. The first time they put us in a room together, everyone's eyes went wide. Here was this very active woman who looked so much like me, there  was suddenly no question where my weight and massive chest size has come from. With the exception of her severe psoriasis, I looked like a younger version of her (the psoriasis showed up for me when I was in college).


There is simply no question that my weight problems are a result of the genetics that I got from that part of my family. Just as there is no question that my little brother was luckier to get the tall skinny genes from another branch of the family tree.

EricVanBezooijen
EricVanBezooijen

Genetics is what makes some people be able to eat anything and not exercise and still not gain any weight, while others have to watch every calorie to manage their weight. However, it's only a predisposition for gaining weight if you do not eat right and do not exercise. You still have to have a bad diet and be sedentary to actually gain the weight. Genetics can't explain the huge difference between the obesity rates in Western countries with sedentary lifestyles and easy availability of calorie-dense junk food and other countries where the population is very active and junk food is not available or is too expensive for the average citizen.

asdjklghty
asdjklghty

@EricVanBezooijen While I agree with what you say, being active a lot means nothing. You might think it's possible to burn off the calories from a Whopper. It is but it comes with a price; muscle loss. The only way to gain weight for most people, is to eat more calories than needed. Exercise can burn some calories but if a person eats, more than he or she needs, weight gain will follow even if they exercise. I know a guy who does swimming, badminton and basketball and he is fat. I could list others I know who are pretty active and they are fat. 

And also, in Asian countries like China, there are lots of fat people. "Western" food can be blamed but if you look those eating the traditional Chinese diet, or kind of traditional diet, you'll see that there are many fat people. Both of my grandpas are from China and they lived in Hong Kong for a while. My grandpa on my dad's side is fat. He doesn't eat western food and just eats traditional Chinese food.

LlordEevil
LlordEevil

I certainly think its a little of both genetics and the environment affecting obesity.  Genetics also affects behavior and because of this alone we would say genetics and obesity are linked.  

apregister08
apregister08

How many people have you seen who are super skinny and have never worked out in their life.  Yes, genetics plays a huge part in this.  It doesn't mean that weight can't be controlled though.

jefnvk
jefnvk

Do I believe there are genetics that may make it a bit harder for some to regulate weight?  Absolutely.  Do I believe that is the reason we have so many morbidly obese?  No.


If genetics is the case, why is obesity a relatively new phenomenon?  Shouldn't we have seen massively obese for the past few hundred years?

JenniferBonin
JenniferBonin

@jefnvkThe article clearly states that most obesity is not caused by genetics:

[“Thus far mutations in about eight genes are known to cause obesity in humans. But these mutations account for under five percent of the obesity in our society, and certainly are not, by themselves, responsible for the current obesity epidemic, since the mutation rate in these genes could not have changed dramatically during the past twenty years."]

peppercmg
peppercmg

@hwilson23 @jefnvk Thats because when those paintings were painted it was considered desirable people to have weight on them, it was a show of fertility, or wealth. But thats only slightly over weight, not obese or anywhere near obese.

hwilson23
hwilson23

@jefnvk For centuries, it was common to find people who were slightly overweight. Just look at works of art; a lot of the depictions include "curvy" (in the thick sense) women and men. Obesity existed also, but not as prevalent. People who were rich were more likely to be fat because they had more money to afford more foods. In the 1600s-1800s in particular, royal or just plain wealthy families would literally feast - every. single. night. 

MarlaShin
MarlaShin

As an adoptee, I have a perspective others don't. My dad was the sort that could eat anything and not gain, Mom is average. I've fought my weight my entire life. . Some time back I tracked down some of my birth-mother's family and for the first time in my life saw blood relatives. At 5'5" and 180 lbs, I'm one of the thin ones. some of it has got to be genetic. 

sweetdigs
sweetdigs

BTW, there's a very good reason USA and Mexico are the fattest countries in the world..and it has nothing to do with genetics. 

sweetdigs
sweetdigs

No, it just seems that way because fat adults raise fat children. 

BradMadiuk
BradMadiuk

No it's not. It means they eat too much. It REALLY IS that simple.

hwilson23
hwilson23

@BradMadiuk No, it's not that simple. Weight varies depending on age, on the simple basis that metabolism slows as you age. For women, it's very different than for men. Metabolism slows due to female hormonal changes in the body after puberty and childbirth, but age is just as much a factor as well. This is not to say diet makes no difference. It certainly does, but there are numerous factors to consider. 

MikeLand
MikeLand

I walk into a rural based Walmart Super Center.  Well, it was scheduled to be a Hypermart until Walmart dropped that designation.  But when it opened, it was, at the time, the biggest Super Center in the USA with 45 cash stands.  On the first day it opened, it did $1.5M in sales.  This Walmart serves an exclusive 10 county region of the state.  So, I'm walking into one of the entrances and see something along the line of this article.  Rounding the end cap of the aisle I see a huge dad with a ginormous electric cart.  He was 600lbs if that.  Then behind him is mom, with her own huge cart.  She was surely 500 and made honey booboo's mom look like Miley Cirus.  Next is the son who has his own card and was surely 300 lbs himself but only around 10 years old.  Then the final member is sister who looks 8 and is 200lbs herself, has really bad edema, and is wearing pop bottle glasses.  I see this family tooling down the front of the store and i could not but help see what they had in their baskets attached to the handle bars.  I see meats, Little Debbie snacks, Coke, chips, and ice cream.  I then think that obesity is not necessarily hereditary unless if the whole family eats the same.

lanbr3
lanbr3

Look at pictures of people (in grade school, high school, adults) from 1950 and 1960.  Kids played outside, adults mostly did some form of manual work.  Wow, almost no fat adults or kids.  

Food stamps started in the 1960s.  There are now 15 means tested food giveaway programs.  A lot of people work in non manual jobs, kids spend all their time on a computer or game machine.  Now kids in grade school are fat, kids in high school are fat, adults are fat.  Wow, I wonder if there could be a connection?

MikeLand
MikeLand

@lanbr3  

You have some good points.  Man, we stayed out to dark 40 and played hard.  We would come home just exhausted and go right to bed and sleep through right until dad came into the room singing, "Oh what a beautiful morning" to wake us up.  We hated it but it did get us up.  If we didn't get up, then he went into the whole song.  We went to school and the physical fitness was like a small version of Marine boot camp.  Yes, we did have Kennedy's physical fitness plan and that meant having to climb that 30-foot tall rope and ring the bell on the ceiling of the gymnasium.  Then on Wednesday night, we went to church and had supper and then went out to the Youth corp.  We played some sport and then went to the service.  Then it was choir practice for our parents and we hit the gym and played like there was no tomorrow.  I was usually covered head to toe in sweat.  We went home and went right to bed.   Fast forward to today and my nephews.  They go to school and there is no physical fitness or PE.  They get out of class and rush home to hook up the Wii so they can game online.  They are only interrupted by supper and then go back and maybe do some homework.  Then they get ready for bed and are restless because they have had no physical activity.  They also go to church on Wednesday night but after the dinner they attend AWANAS where they regurgitate their bible verse and then get their lollipop.  Then its service time and then they go home to the Wii.  Neither of them can run all that well because there has been no time in their lives where they had to actually run.  They can't toss a ball to save their lives and if there is a wifi loss in the home, they get horribly depressed and bored.

jagonzo1962x
jagonzo1962x

@lanbr3 Even in the 70's and 80's people were skinny. Do remember Farah Fawcett? That was how a lot of woman looked back in the 70's. 

vgupta123
vgupta123

@lanbr3 Thank god for photography in the 50s and 60s. Otherwise, the experts would tell us that obesity rates haven't really risen so fast (because fast rise contradicts the genetic explanation). Rather we now have better technology to diagnose obesity.

peppercmg
peppercmg

@lanbr3 But you forgot how much more processed food we eat now too.... mix that in and how do we expect to be healthy? Even in the 60s they liked their fatty casseroles but at least they were more or less home made and worked off by more activity. Now we eat Way worse and do way less, now thats a recipe for disaster 

MikeMcEwen
MikeMcEwen

In the end, isn't it calories consumed vs. calories burned?  I Would think that even a person w/ the defective gene could control his weight if he control his diet.

RekkaRiley
RekkaRiley

@MikeMcEwen 

It is no where near that simple for most people.

Stored fat is what allows human beings to survive periods of drought and famine.  It is what allows women to be able to successfully carry a healthy fetus to term and nurse that child afterwards, which is why anorexics and extreme athletes often stop having their periods altogether; their body doesn't have enough fat to support a baby, it knows it, so it's trying to make sure the woman doesn't get pregnant when they clearly don't have the physical means to carry it to term without killing themselves.

Your genes have millions of years of data that says "We have to have this minimum amount of fat in order to survive, if we go below that threshold it means we are out of food and we need to hang on to every calorie we can get!"

This threshold is different for every individual.  Some people have a higher threshold, others have a fairly low threshold.  It's not a hard and fast rule, more of a spectrum, but in general, you see the following trends:

-Women have a higher fat threshold than men, so men can lose a lot more weight before hitting what many doctors and personal trainers call "the Plateau."

-People whose ancestors came from colder, harsher climates tend to have higher thresholds than people whose ancestors came from warmer, milder climates.  This includes many people of Northern European descent (i.e., a majority of white Americans), people of British, Scottish, Scandinavian, etc. descent.  Compare this to white Americans who are mostly of Central, Western, or Southern European descent:  French, Spanish, Italian, German (Germany sits between North and Central Europe), Greece, etc.  They tend to have a much lower threshold, thanks to a longer growing season and milder winters. They could afford to lose more fat, because they could still find food during the winter; their counterparts in the frozen north could not.

If you have a certain threshold for fat deposits, and you try to push past that, your efforts at losing weight will often backfire.  Instead of losing more weight, you suddenly start gaining more weight, despite "doing everything right."  This is because your body is in a panic, it thinks that the loss of the fat means there is a famine and if it doesn't save what's left than you will starve.

You might know better, but your body does not.

A better benchmark for health is your heart, your lungs, and your bones.  Keeping your heart rate and blood pressure within a certain level, keeping your lungs clear and healthy, and maintaining healthy level of bone density should be the true goal of diet and exercise, NOT the amount of fat on your body or the number on a scale.  Trying to force your body to drop too much weight can negatively impact your heart and bones, and thus is ultimately counter-intuitive.

peppercmg
peppercmg

@MikeMcEwen Its ALMOST that simple. Rekka who replied to you is making it sound like its not by talking and talking and talking... Everyone is different, some people have more natural muscle.... (normally men) so they burn calories faster. Some peoples metabolisms are just kind of slow.... But those people can boost them with a little effort like taking certain vits and working out in the morning, eating the right kind of breakfast ect. Over ALL though if you control your calories to something that is around healthy, and exercise you will lose weight. A lot of people just dont hold themselves accountable. Like.... "ive been dieting for 3 weeks and havent lost any weight!!!" (mean while they had 3 sodas that day) Or they do silly crash diets like eat nothing but one thing for a month, pig out for 2 months then blame dieting. A diet for LOSING weight should be healthy and something you can maintain and when you stop it, you DONT stop it you ease up a tad. Fact is you cut calories and work out. You could starve yourself but you will lose it in a dangerous way to your body, and will probably gobble up food when you stop starving and yo-yo... But if you cut calories in a healthy way, like I dunno ..... eat some home made chicken noodle soup as a meal one day with 1-2 pieces of toast and a glass of water instead of a cheese burger, fries and soda..... you are lying if you say you wont lose. Some people just lose a bit faster.

MikeMcEwen
MikeMcEwen

My question is:  Can even people w/ this gene problem be able to lose weight under the proper setting.

TerenceP.Brashear
TerenceP.Brashear

@radjacks@RekkaRiley@MikeMcEwen
 

Rekka sounds like Marilyn Wann........all her science comes from fellow bloggers and not clinical work that is subjected to peer review.

The article is discussing obesity:

"Obesity means having too much body fat. It is not the same as being overweight, which means weighing too much. A person may be overweight from extra muscle, bone, or water, as well as from having too much fat."

Having too much body fat it obesity and is clinically proven to not be healthy.

JenniferBonin
JenniferBonin

@MikeMcEwen Yeah, I was wondering that as well.  I mean, if your body literally won't burn fat, that's got to be tough.  Because it implies that the only way to even possibly get rid of that fat build up is to literally starve yourself -- and even then, I'd be interested in finding out how well it works.  What's the chemical mechanism preventing the fat from being broken down, I wonder?

peppercmg
peppercmg

@MikeMcEwen Yes they can. These genes are given wayyy to much credit. They dont make that big of a difference, like okay (fat gene girl A) may have naturally slightly thick thighs she will Not have rolls coming from her upper thighs to her knees though. (fat gene girl B) Might have trouble losing weight as fast as her friend, but if she sticks with it she will lose weight eventually. Some people just simply can not be size 00 (though imo thats another health issue) But everyone can be a healthy-ISH weight. People who are morbidly obese who eat steamed veggies and grilled chicken breast if they even exist its like those rare cases of strange medical issues. Some people are bigger because of medications.... But even they probably wouldnt get morbidly obese just because of meds, they are prob gobbling down fast food as well. Most of it is people lying to their friends, and to themselves and using any excuse and trying to build it up to look like something more.

radjacks
radjacks

@RekkaRiley @MikeMcEwen 

Your comment about midsection fat providing some benefit to the hard laborer has zero foundation in science.  Yes, the body does need some fat and other energy to survive, but beyond a certain small amount, people are just overweight. Period.  Your views, while long-winded, sound uninformed and borderline quack-ish.

RekkaRiley
RekkaRiley

@MikeMcEwen

The point should not be "losing weight."

The emphasis should be on whether or not your internal systems are healthy.

Human beings have to have a certain minimum level of fat to stay healthy.  Fat insulates the body, provides cushioning and support for muscles and bones, and provides a steady supply of nutrients in order to avoid sudden drops or spikes in blood sugar during times of famine.

Take a look at professional, Olympics-level weightlifters versus people who do hard labor for a living and professional body builders.  Body builders have a  lot of impressive muscle and little to no fat, but their muscle is ultimately useless; it is for show only.  People who work hard labor, with a lot of heavy lifting, are quite muscular but often have a significantly higher amount of fat, especially around the midsection.  This fat is important because it provides additional support and cushioning, and increases balance by lowering the center of gravity to allow the individual to lift heavy loads above their head without causing them to fall, or causing their back to snap backwards. 

This is also why women in general tend to have better balance than men:  your center of gravity is usually wherever the widest point in your body is, which in turn is usually the point where you carry the bulk of your weight.  For women this is usually in the hips, whereas for men the center of gravity is much higher, near the chest and shoulders.  The closer your center of gravity is to the ground, the more stable you are and the better your balance.

Professional weight-lifters fall between these two extremes:  More muscle and less fat than hard laborers, but way more fat and less clearly sculpted muscle than body-builders.

Here's a great visual guide to "beef," that summarizes these differences (you have to click on the thumbnail image to make it big enough to read):

http://coelasquid.deviantart.com/art/Abdomination-How-to-draw-beef-132538271

There are copious amounts of snark there, just as a warning.