NOVA scienceNOW : 22 – Obesity
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NOVA scienceNOW : 22 – Obesity

March 8, 2020


NEIL DEGRASSE TYSON: Okay, we talked about
bungee cords, that stretchy force that binds protons and neutrons. They’re kind of like
springs. Of course, what’s great about springs is their
flexibility. With some effort, I can stretch it, or I can make it smaller, at least for
a little while. But it always bounces back to a certain predetermined size. Well, according to some researchers, people
might be like this, too. No, matter how hard we struggle to lose weight, our bodies will
keep bouncing back to about the same size. And as David Duncan reports, that size might
be predetermined by our genes. DAVID DUNCAN (Correspondent): We are what
we eat. And as we eat more and more, many of us gain weight we’d rather not have. But
for some people, like Teresa Godfrey, the compulsion to eat is a lifelong struggle. TERESA GODFREY: I try and control it as much
as I can, but there are days that I cannot control it. And I just eat and eat and eat
and eat, and I don’t know when I’m full, really. And I’m aware that I’m doing it, but I can’t
stop it. DAVID DUNCAN: Since childhood, Teresa has
faced ridicule, embarrassment and blame for being overweight. So has her only son, Jake. TERESA GODFREY: Parents in the playground
used to look over and look at me, because I’m big, Jake’s big, and just, thought that
we sat there all day and ate food, basically. ELANA (Addenbrooke’s Hospital): (I was just
going to ask you a few questions. SADAF FAROOQI (Addenbrooke’s Hospital): Patients
like Teresa and Jake, have had, really, a very tough time, from a very young age. They
have often been blamed for being overweight and obese. And it’s amazing how we fail to
see that, actually, being overweight and being obese can be due to a biological reason, can
be due to your genes. DAVID DUNCAN: Suppose you could prove that
for certain patients, it’s not lack of willpower that causes obesity, but the lack of a chemical
inside the brain which tells us to stop eating? That would be no surprise to Jeffrey Friedman,
an obesity researcher at Rockefeller University in New York City. Friedman believes that for
each of us, eating behavior is, to a large extent, hardwired by our genes. JEFFREY FRIEDMAN: What makes some people weigh
350 pounds and other people 150 pounds? To a very large extent, those are genes. And
each of us are, to a large extent, predetermined to be at a particular weightósome people
heavy, some people thin, most people in between. DAVID DUNCAN: So we have very little control
over our weight… that there’s a set point. JEFF FRIEDMAN: The set point defines a range
for each person, and people can operate comfortably within that range. But the further one wants
to deviate away from the set point in either direction, the more difficult it becomes.
So that if you’re at your stable weight and you want to lose 50 or 100 pounds, it is very,
very difficult over the long term. TERESA GODFREY: I lost 35 pound in between
eight and nine monthsófound it very difficult, but did lose it. But it went back on. As soon
as you stop dieting, it just goes straight back on. JEFF FRIEDMAN: For obesity, the evidence for
a number of sources would suggest that it’s 70 to 80 percent genetic, which is the highest
hereditability that’s been recorded, with the possible exception of height. DAVID DUNCAN: Twenty years ago, Friedman began
experiments to uncover the genetics behind the hunger drive, trying to discover why certain
lab mice are born with such a compulsion to eat that they become almost too fat to walk.
Then, in 1994, Friedman and his collaborators made a groundbreaking discovery: these obese
mice lacked a previously unknown hormone which signaled the brain to stop eating. Friedman
named it leptin, after the Greek word for thin. JEFF FRIEDMAN: Leptin is a hormone, made by
your fat, that circulates in the blood, that then sends a message to your brain reporting
how much fat you carry at a given point. DAVID DUNCAN: The five milligrams of leptin
in this bottle are 10 times the amount that can circulate in our bloodstream, where it
acts like a thermostat to tell the body if it’s starving or if it has enough fat to survive.
How it works becomes clear when you see an animal genetically altered to produce no leptin
at all. JEFF FRIEDMAN: You’ll notice a few things
about these animals. One, obviously this animal is a lot larger or heavier. That animal is
moving around everywhere, and this animal hardly moves at all. The only difference between
these animals is a defect in a single gene, the gene that encodes for this hormone, leptin. DAVID DUNCAN: And how does this relate to
humans? JEFF FRIEDMAN: Humans have the same hormone.
And when humans are lacking this hormone, leptin, as is this animal, they, too, become
massively obese and eat more. It turns out that this animal, because it lacks leptin,
never gets the signal that it has sufficient fat, and thinks it’s starving. Now if you
were to give this animal leptin injectionsóreplace the leptin it can’t make on its ownóthey
eat less, they lose weight, their fat content goes down. DAVID DUNCAN: Friedman’s discovery created
a sensation. Was this the Holy Grail for the overweight, a possible cure for obesity? STEPHEN O’RAHILLY: I remember, precisely,
the day I read the Friedman paper. And the hairs on the back of my neck stood up, because
I thought, “My word! This is a real insight into how body weight is controlled.” DAVID DUNCAN: Unfortunately, when leptin injections
were given to obese human patients, most of them did not lose significant amounts of weight.
Still, Stephen O’Rahilly, director of the obesity clinic in Addenbrooke’s Hospital,
in Cambridge, England, believed that Friedman’s discovery held an important key to human appetite,
if he could understand how leptin worked. STEPHEN O’RAHILLY: Leptin does something to
the brain. It suppresses appetite; it does it through a series of steps. DAVID DUNCAN: Once leptin reaches the brain,
it turns off cells that increase appetite and turns on cells that decrease appetite,
in a dual action that suppresses hunger. A central switching component in the leptin
process is the melanocortin 4 receptor or MC4R, which receives and passes on the message
to damp down hunger. If these receptors are altered by genetic mutation, their surface
becomes malformed, unable to process the message to switch off appetite. STEPHEN O’RAHILLY: It would be very difficult
to be a patient with one of these mutations, try to get slimmer when your brain is screaming,
“You are hungry. You must eat.” TERESA GODFREY: You’re just ravenous, and
you just have to eat. And you can’t stop. Some days you can’t stop eating, and you’re
on and on and on. JAKE GODFREY (Obesity Clinic Patient): So
you just eat anything, until you’re just full up. And then you just…you regret it. It’s
like, it just takes over you. TERESA GODFREY: Until you actually physically
begin to feel sick. And then you think, “Well, why did I eat all of that food? Why? I didn’t
really want that. Why did I eat it?” DAVID DUNCAN: Eight years ago, Teresa Godfrey
came to the obesity clinic in Cambridge searching for answers. SADAF FAROOQI: They have always known that
there was some reason why they were always hungry. They have always thought there was
some reason why they gained weight more easily than others. And effectively, what we’re able
to do, is to provide for them an explanation for that. DAVID DUNCAN: The new scientific breakthrough
is understanding the gene that codes for the MC4 receptor. Teresa’s gene has a mistake
that causes her receptor to grow incorrectly. SADAF FAROOQI: When we actually look at the
gene in the lab, what we find is one particular one of those building blocks is actually different.
And that’s enough to stop this gene making a receptor that works. DAVID DUNCAN: Sadaf Farooqi extracted Teresa’s
DNA from a blood sample, and then put it through a process to isolate the gene that encodes
for her MC4 receptor. SADAF FAROOQI: And I think, when the MC4 is
done, we need to think about which other genes might be relevant to these patients. DAVID DUNCAN: This gene was then amplified
and inserted into a living cell in Farooqi’s lab, which then grows Teresa’s receptor in
a flask. SADAF FAROOQI: And when it’s in those cells,
those cells can actually be grown up and can actually behave in the test tube as if they
were in Teresa’s body. So, essentially, in this flask are some cells which grow up and
express Teresa’s MC4 receptor on their surface. We add the hormone that normally activates
the receptor. So, basically, the hormone should dock on the receptor and give us a readout. DAVID DUNCAN: A normal MC4 receptor reads
out 100 percent; but Teresa’s malformed receptor reads out zero. SADAF FAROOQI: So Teresa’s receptor is really
non-functioning. DAVID DUNCAN: Measuring Teresa’s mutation
has allowed the doctors at Addenbrooke’s, for the first time ever, to use genetics to
accurately predict how much a patient will eat. SADAF FAROOQI: Basically what we can show
is that the defect in a single gene, in a single molecule, and how it behaves in the
lab determines the amount of food people will eat at a single meal. ELANA (Addenbrooke’s Hospital): Hi. I’ve got
your lunch here, and you can have whatever you like. SADAF FAROOQI: We find that a person who is
of normal weight, and whose MC4 gene is working normally, might eat somewhere in the realm
of about 4- to 500 calories, when allowed to eat freely. Teresa, and with Jake, in fact,
they would eat probably two and a half or three times as much. TERESA GODFREY: Dr. Farooqi phoned me and
told me the results, and I cried on the phone, because I was just so relieved. I cried for
Jake, not for me, more so than anything else. STEPHEN O’RAHILLY: Jeff Friedman’s discovery
of leptin, in 1994, was a phenomenal catalyst to, not only my work, but the whole of the
field. This was the first time that a real molecule truly was regulating body weight
in mammals, and we went on, then, to show that obviously it was relevant for humans,
too. DAVID DUNCAN: How many people have this MC4
receptor problem, and how does it compare to other genetic disorders? STEPHEN O’RAHILLY: Our best estimate so far
is that around one in 1,000 people carry a mutation in MC4 and are obese. That means
that, worldwide there’ll be tens if not hundreds of thousands of people with this, with this
disorder, so it’s not, not by any means, rare, and it’s certainly commoner than some well-known
genetic disorders such as muscular dystrophy or cystic fibrosis. DAVID DUNCAN: Do you worry, that people will
look at this and say, “Aha, it’s not the, you know, the Big MacsÆ; it’s, it’s genetic.” SADAF FAROOQI: Clearly, if you eat fast food
all the time, and are very sedentary, whatever your genetic makeup, you are going to gain
weight. Clearly, if you have genes that predispose you to gaining weight, you’ll gain even more.
So it’s always a balance of the two. I think even people who are overweight or obese and
don’t have an MC4 gene problem, they will have other genes that are contributing to
them gaining weight very readily. DAVID DUNCAN: Scientists are already identifying
other genes that contribute to obesity. The hope is to create medications that can help
people who have these genes maintain healthier weight. But until then, overweight people
should try to maintain the lowest weight their biology will allow. JEFF FRIEDMAN: People should do what they
can to improve their health, and that would include being at the lower end of their range,
exercising, eating a heart-healthy diet. So I think we need to focus on what we can do
and improve health to the extent of our ability, but not criticize people because they can’t
lose hundreds of pounds. It’s their biology that makes it difficult to lose those hundreds
of pounds, not some personal failing. TERESA GODFREY: When I found about the MC4R,
it was a relief, a relief and a release, to know that actually, yes, it’s not all my fault,
and there’s a reason for this happening to me. I’d just like to be as I am now. I’ve
accepted who I am. If you would say to me would you rather win the lottery, or would
you rather find out about MC4R, I would say MC4R any day. You can keep your money.

Only registered users can comment.

  1. This is bull shit. Americans are fat because they eat too much, and eat too much of the wrong foods, and don't get up off their fat asses and move. Are we supposed to believe the American's gene pool is different and that explains why Americans are fat while other countries that are not gluttons have the skinny gene? PLease this is all excuses.

  2. Holy FUCK the ignorance here. Just "stop eating" won't work. Some people's metabolism are affected by genes, and eating less would give you more fat than if you ate more with a normal metabolism.

  3. Good point actually. The Ethiopian kid doesn't have access to cookies, sugar, fruits. The Ethiopian kid you're referring to, consumes barely enough to survive. This is not the case with other regions of the globe. Even in some regions in Africa, where fat people were never heard off, now there are plenty of obese people and diabetics.

  4. A close acquaintance of mine started jogging 6 miles per day, working out with Spark People and Insanity. She measured her daily calory intake to be less than 1500, yet she gained 4 pounds in a single week, and 2 pounds the next week, when she just replaced some fats in the diet with apples and grapes. Now she's losing weight without working out. It's all in "what you eat", not "how much you eat".

  5. The genetic argument is flawed. People have always had genes. Yet, this obesity pandemic began raging a little more than 28 years ago. So, what happened? Did the Fat gene suddenly infiltrate the masses to create this fat plague? Americans are eating themselves to death to the tune of 5,700 obesity related deaths PER WEEK!!

  6. Another incomplete shit pseudo documentary. They fail to understand why obesity only started 30 years ago. The reason is simple: high sucrose corn sirup which has been mass produced since the seventies and found its way into soft drinks and processed foods. It impacts leptine and makes you feel hungry. The solution is not that hard: dump the soft drinks and processed foods and get your fructose through natural products. E.g.: fruits (not juices). And ffs ignore the low fat bullshit.

  7. The entire low fat industry is bullshit. Sugar and carbohydrates are the cause of obesity. Enjoy your bacon and eggs. Go easy on rice, pasta, bread and potatoes and refuse soft drinks and processed foods. You'll feel and look fine in no time.

  8. There is no one stand in front of these people shoveling food into their mouths, they do that all on their own.  They also make the choice of what food to graze on and are the only ones who can make them get off their asses and exercise.  The idea of a dithesis which is a combination of a genetic factor along with an environmental one still relies on the fact that the person is cramming food into their faces at an out of control pace.  I have friends that are obese and they will all claim that they don't eat all that much, but they are constantly munching on something and eat more than any two people should eat when they sit down for a meal.  People are not like plants whereby they absorb carbon from the air to produce their mass, we consume all of the caloric materials through our digestive tracks and the only regulation of intake is at the mouth.  When a child is obese, it is the sole responsibility of the parent for making them that way.  Genetics aside: fat kids eat like pigs with the help and encouragement of their fat ass parents.  Once a person grows the fat cells, they will always be with them, the only thing they can do is to loose the fat from the cells, so when a parent feeds a kid like they're fattening them up for market, it is their fault that their child will have to live the rest of their lives trying to keep the balloon from re inflating.. 

  9. Wow! How can experts be so wrong. The truth is that a palatable diet INCREASES your fat set point. This is well established in the scientific literature. If you want to lose weight and maintain that weight loss, then you have to eat a bland diet (or at least a less palatable diet).

  10. I've seen the stupid comments here. I suffer the same plight. I can lose weight but, I have to endure tremendous hunger pains at bed time. If i don't feel like I am starving , I won't lose weight. People that eat something. It tides them over. I get severely hungry in an hour. Doctors have put me on restricted calorie diets in the hospital for 3 weeks and I gained weight, much to their surprise. Used NutraSystem and never lost a pound. Easy to say when you are not me.

  11. A friend of mine has hyperthroidism. It is a chemical hormone controlled by a gene. He eats like a horse and doesn't gain weight. Why can't he gain weight if his body consumes all those nutrients. It's metabolism stupid people.

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