In the previous blog of this six-part series I concluded
that increased sugar consumption in general, and sugar sweetened sodas
specifically, seem to account for a large amount of our obesity. And obesity is correlated with a suite (no
pun intended) of conditions known as “metabolic syndrome,” of which diabetes is
not only associated but may be, in some cases, reversible with weight loss.
Same can’t be said for cardiovascular disease, it appears.
So, it seems the major reason for obesity in the world and
the U.S. specifically is excess calories, of which sugar would be the major
contributor to the epidemic.
Although the above reasons may be the major cause of
obesity, there are factors other than consuming too much sweetened soft drinks—such
as particular genes, unique gut flora, or perhaps even viruses.
It appears that genes play a major role in obesity. Now, this does not mean that the increase in
obesity in the last 50 years in the US or worldwide is due to an increase in
obesity genes. In order for that to have
happened there would have to have been a selection for obesity—that is, obese
people having more children. And even if
that were to have been the case, of which there is no evidence, there would not
have been enough time for this to have had much of a measureable effect.
So, the presumption is that the (recent) world population
has always had the same genetic potential to become obese—certainly over the
last couple hundred years, anyway. But
some people may have more of a tendency towards obesity than others. Certainly
in our own anecdotal experience some people seem to eat and remain thin, while
others have a difficult time keeping the pounds off.
Now, for us here the interesting question, or at least the
question that interests me, is: HOW MUCH do genes influence obesity?
For geneticists, getting a handle on this would almost have
to start with a concept known as “heritability”—or in other words, how much do
genes influence the trait in question.
It is intuitively obvious that many traits are influenced by
both the genes and the environment.
Other traits would not be influenced by the environment. If we look at
eye color, we’d say that the environment does not affect it very much;
geneticists would say it is highly “heritable”—it really doesn’t matter what
your environment is like. Your eye color
is going to depend on what kind of genes you have, not by what kind of environment
you grow up in. Another is your blood
type. For traits like this we’d be safe
to say that heritability (h) is “1.0” (h ranges from 0 to 1.0). However, for other human traits, like
alcoholism or schizophrenia or some reading disabilities, it is easy to see
that there would be an environmental influence.
For example, an estimate of “h” for personality is 60%, meaning that 60%
of the total variation for personality is
due to genetic causes, and 40% is due to the environment.
We have to be careful of our interpretation of this 60%
value. What it means is that when you
look at a particular group of people (those that were examined for their
personality type), and measure all the types of variation that exists for a
particular personality trait (of which there would be a lot!), 60% of the variation
is due to genetics, and 40% is due to environmental influences. The “h” value DOES NOT apply to
individuals. It doesn’t mean that YOUR
personality is 60% determined by genes and 40% by the environment.
Now, heritability estimates have been done for years over
many many characteristics, in everything from fruit flies to chickens to corn
to humans.
So, how do we estimate heritability?
It turns out that for humans, there is a wonderful genetic
“tool” known as “twins.” As we all know, identical twins are genetically
identical (for all intents and purposes for our discussion (critics please
don’t get all excited about epigenetics—a whole other discussion), while
fraternal twins are no more genetically identical than another sibling. So, you can see that if you looked at
identical twins, which are genetically identical, and measured some trait, such
as personality, ANY variation in their personalities would be due to their
environment. Conversely, if you looked
at fraternal twins, which only share ½ of their genes—like “normal” brothers
and sisters—their differences in personality would be due to both genetics and
the environment.
So in this way I think you can kind of see that by examining
both types of twins you can make an estimation of “h”. So, what do they find when they look at “h”
for obesity?
Since 1997 many twin studies have found that variation for
BMI (and recall from my Obesity-1 blog how inaccurate that is) has a strong
genetic basis, with “h” ranging from 0.55 to 0.85 (remember, where 1.0
represents 100% control of the trait by genes).
Now, most studies have looked at adult twins. A problem with this is that the older a
person is, the more influence the environment may have. However, by looking at children, in theory,
you’d get a better estimate of “h” because, well, your results would not be
influenced by years of environmental “entanglement.” Or in other words, adults
have lived longer in an “obesogenic environment.” (I’ve just been waiting for
an excuse to use the word “obesogenic”!).
A 2008 study in the United Kingdom looked at 5,092 twin
pairs aged 8 to 11 years old, with an average age of 9.9 years. BMI’s were determined, as well as waist
circumference (a better measure of obesity).
What did they find? “h” was 0.77 for BMI and 0.76 for waist
circumference.
So the conclusion here is obvious: as with other studies,
genetics has a majority influence on obesity.
But I just need to make a quote from this 2008 paper, as
their words are much better than mine:
“The fact that siblings’ experience of being
served similar food, being given the same options for television viewing and
active outdoor play, seeing the same behaviors modeled by parents, and going to
the same school does not make siblings more similar is a challenge for etiologic
models that highlight the home environment as the root cause of obesity. This
finding will, however, come as no surprise to parents, who are well aware that
their children come in different shapes and sizes despite having a similar
upbringing.…. Results from the present study highlight the fact that excessive
weight gain in a child is unlikely to be the fault of the parents and is more likely to be due to the child's
genetic susceptibility to the obesogenic features of the modern environment.” (Emphasis mine).
Now, I may quibble a bit with these authors in terms of not
blaming the parents—I mean, who else is responsible for a child’s “obesogenic”
environment? Seems to me that if it is
observed that a particular child has a predilection for gaining weight the parent
can intercede and restrict that child’s caloric consumption. Now, the “fairness” of this in child rearing
is another matter, but certainly a parent could restrict calories, at least up
to the point they have control over the child’s ability to sneak off and buy
soft drinks, for example. But, being a
parent of six I recognize this as easier said than done!
We digress here! The point is that a CULTURE that supports
unrestricted caloric consumption, which ours does, will lead to obesity—and
some will gain faster than others. But
we will ALL probably get fatter.
Well, if genes control our tendency to get fat, the next
question for a geneticist is: “Just WHAT genes are those?”
Around 20 genes have been implicated so far in controlling
obesity. Two of them have received
recent press: the FTO gene, the KSR2 gene, and the IRX3 gene.
The FTO gene was the first to be discovered in 2007, and it
is associated with increased food intake, not energy expenditure. A recent 2013 study reports that the FTO gene
may do this through the hormone “ghrelin” (a hormone produced by gut cells to
stimulate hunger)—people with the gene found high calorie food (particularly
fat) more desirable and were hungrier than those that don’t.
Further, a 2013 study showed that MRI brain scans showed that
people with the FTO gene showed brain activity in areas associated with
motivation to eat remained high before and after a meal.
However, it is also a good example of how the genetic control
of obesity is probably controlled by hundreds, if not thousands, of genes, and
FTO’s effects are “minor,” since it only accounts for around 6.6 pounds of
excess weight compared to a normal person without this gene. Interestingly, it is found in 45% of
Europeans, 52% in West Africans, and 14% in Chinese/Japanese.
In March of 2014 it was reported that the IRX3 gene may be
the main controlling of the FTO gene.
This further illustrates the complexity behind the genetics of obesity.
The KSR2 gene has been found to impair fatty acid and
glucose degradation. Presumably, neither
fat nor glucose is broken down and therefore they are converted to stored fat
instead. This is the first time evidence
has been shown that obesity is due to “slow metabolism.” However, only 2% of obese individuals have
this gene, so it certainly does not affect a majority of the obese
population.
And so, it is clear that the future of such studies will
uncover many more genes, perhaps even those that have more major effects. And perhaps now that specific genes are
known, new drugs can be developed that target these specific sites.
It is easy to speculate that humans have had selection for
the ability to get “fat” during times of plenty, in order to make it through
lean times. It doesn’t take much of an
imagination to picture a tribe people huddled in a cave, completely cut off by
an extended, severe snowfall, running out of food. Certainly under those conditions the fattest,
and those with the slowest metabolism, would have the greatest probability of
surviving and living to pass on their “fat” genes. Us skinny folk would not be so lucky under
those conditions. Conversely, during times of plenty those that got fat the
quickest would be those that would have the ability to survive the lean times.
Today we reflect the genetic selections that have taken
place over the last 50,000 years of Homo
sapiens time on this earth—we are just cave men dressed in suits with a
genetics designed for survival under conditions that don’t exist any more.
In our obesogenic environment our bodies just yell “Hooray!”
and get on with getting fat—because, well, that’s what they’ve always done.
Looks like this obesity series will extend to at least one
more blog—I can hardly leave the topic without looking at diets, which I’ve not
been looking forward to: I can hear comments now. Atkins Diet is the best! No, Paleo is for me!
No, no, it’s the South Beach diet! And so on.
Useful References
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