“The Science of Obesity: Fighting Fat with Fact” presented by Dr. Susan Bagby

“The Science of Obesity: Fighting Fat with Fact” presented by Dr. Susan Bagby


DEB: Before we get
started formally, I just wanted to give you a little
explanation behind the word cloud, behind me. When you all registered,
you indicated what topics you were most
interested in hearing about, related to these topics today. And we did our best to
try to coalesce them into some way, shape, or form. And I think you can see
the variety of things that people are interested
in learning about. We may not get to every
single thing on here, I can guarantee you that
carbohydrates, obesity, fat, sugar, childhood, is going
to get addressed, but we’ll see how far
and wide we can go. Our set up today is that we’re
going to start with one speaker. After the speaker, we’ll have
time for question and answer. We’ll take a break. And then we’ll come back and have
our other two speakers, again, with time for question and answer. And then depending at the
end, if there’s still time, we’d love to be able to
facilitate as much question and answer as possible. So our topic today is, Fats
Aren’t The Whole Story: The Future of Obesity Prevention. That’s really our focus. And we’re looking at it from
a multigenerational aspect. I’m very excited to
introduce our first speaker. Dr. Susan Bagby is a
physician, a nephrologist, and Professor of
Medicine and Physiology, Pharmacology at the Oregon
Health and Science University. Her academic medical
career is focused on patient care in the areas of
hypertension and chronic kidney disease, teaching principles
of medical pathophysiology, and clinical practice to
students and residents. She has received NIH
and VA merit-review funded research in Mechanisms
of Developmental Hypertension. She’s served on National Review
groups for the American Heart Association, National
Institute of Health, and National VA Career
Development Program. She recently served as
an invited participant at an NIH-wide science visioning
process, designed to focus on health disparities research. Her ongoing research centers on
pathways of nutritional programming in early life as a cause of
hypertension and kidney disease in adolescence and adulthood. Dr. Bagby currently serves
as a founding member of the steering committee of the
Bob and Charlie Moore Institute of Nutrition and Wellness at OHSU. She heads the institute’s community
education and outreach effort, currently focused on
developing and disseminating enrichment nutrition curricula
for youth and young adults. Welcome Susan. And while we’re getting
her slides up and running, just want to also
remind those of you who are live-streaming, that we
will be monitoring your questions, digitally. And we will try to
ask some of those, as well as providing opportunities
for folks here in the room. We’ll do our best to get as
many in as we possibly can. SUSAN BAGBY: Thank you so much, Deb. AUDIENCE: [INAUDIBLE] SUSAN BAGBY: I’m
delighted to be here. It’s often difficult for
me to project, so raise your hand if I get softer. This is the second
year that we’ve done this, the Moore Institute and
Deb’s group at PCC Food Nutrition. We are thrilled to do it and
hope this is going to be ongoing. We are, of course, dedicated to the
message of early-life nutrition, and how that impacts
health down the line. And so, the degree to which
PCC’s wonderful facilities magnify and disseminate that
message, is really powerful. So, thanks Deb. OK, let’s see if I can
figure out how I’m going to, I think I’m going to use this. So, Science of Obesity:
Fighting Fat with Fact, here’s what I’m going
to try to do, roughly. A little bit about the obesity
epidemic, which you all know about. And then, focus on the
biology of obesity, the fact that it really is a manifestation
of the developmental processes that go on in early life. We’re going to look at how both
under-nutrition and states have over-nutrition in
fetal, or early life, can program the development
of chronic disease. I’m going to get you into
some of those mechanisms of chronic disease. You’ll see in my pathophysiology
background peeking out. And then, I want to
talk to you about how those things that
are programmed can be passed down to future generations. And really, the fact that this
is a crisis for the 21st century. So, the epidemic of obesity. You can see here, a graph. I copied this, so it’s not perfect. But these are the rates of obesity,
as a percent of the population. The top two bars are
men and women in the US, the bottom two
dashed-bars are global. And you can see that, and really
it’s coming from about 1965, but mark 1975, and
you can see over time the increase in the incidence of,
really that’s the prevalence of, obesity. And then it’s projected beyond
2014, when this was published, on out to levels that you can
see for the United States, are around 40% plus. This has increased in a way
that no one has ever seen, except in infectious and
communicable diseases, and yet this is a
non-communicable disease. So we were really
caught short-handed in terms of understanding this. So how did we get here? What’s happened? I’m old. So I’ve lived through it. And things have changed dramatically
in so many different ways. If you think about
the attitudes that have come across over that
time, on the way to the truth, the saturated fat is bad. We started with
that, that was right. Unfortunately, that got
twisted to say all fat is bad. And then that led to
a frenzy, if you will, of low-fat diet and high carb. And even if you weren’t
trying to do high carb, if you’re on a low total-fat,
you’re going to do high-carbs, just to get enough to eat. That proved to be totally
ineffectual in terms of reducing the cardiovascular
risk that we were getting after. And then, about that
time when fat looked bad, the sugar companies thought,
oh this is our chance. Sugar is good. And, as you all know,
we’re inundated, still, today with sugary products
that we’re fighting very hard to do something about. And I couldn’t resist putting,
fruit-juice sugar is better, because that’s what my daughter
thought, no matter what I said. So one of my
granddaughters literally got rotten teeth, because fruit
juice was considered good. It’s an amazing story. Food culture has changed. Portion sizes, processed food,
eating out, food knowledge has declined. We’ve lost our food culture. And certainly, the
convenience culture has cut down on how
many steps we take a day, cars, TV’s, remote controls,
online services, all of it contributes to our sedentary state. So that’s how we got here. But up until about 1990, practicing
medicine, I’m in the clinic, and people are coming in, and we
begin to see this in the clinics. This increase in a group
of diseases that we did not understand why this was happening. We had only two ideologies, if you
will, of these chronic diseases. One, it’s genetic. Although, that wasn’t
really very helpful, and we couldn’t do
anything about it. And the other, was the choices
that people were making in terms of their diet and exercise. And of course, in that period
of time, it was all your fault. That turned out to be wrong. And in fact, during
that time, we were so impressed with
this conglomeration of disease entities coming
together in the same person, that we made up a syndrome. We made up a new entity that we
call Syndrome X. And ultimately that’s evolved to what we now
know as metabolic syndrome. And that consists of visceral
or intra-abdominal obesity (specifically, not generalized),
high-blood pressure, increase in your
triglycerides, reduction in your good HDL cholesterol,
and impaired fasting glucose. All of these things
were happening together. And then in 1990, there
was a paradigm shift. And that came from somebody many
of you here, knew and loved. His name was Professor David
Barker, he was part time at OHSU, for the last 10 years of his life. And it was a wonderful treat
for us to work with him. What he did over a period
of close to 20 years, is learn and teach
us that environments that you’re exposed to
in early life, in fact, can change your body, can
alter your physiology, change your organ structure, and
the way your body expresses genes. And that can, in fact, program
how you function in later life. And increase your risk
of chronic diseases. And those diseases that I’m
going to talk about today, are those that come under the
metabolic-syndrome category. So we had an old
definition of obesity that had to do with BMI,
body mass index over 30. That was it. Now, we see obesity as
a late manifestation, a late manifestation, of a
progressive, multisystem metabolic dysfunction. And it’s initiated in early life. It’s initiated by adverse
environmental exposures. And it’s defined by this excess
in visceral or inter-abdominal obesity. And it is just one component
of the metabolic syndrome. So we no longer see
obesity as a standalone. So what is this
process through which early environments programmed
the body to behave differently in subsequent life course? Well, the concept is that it’s
a normal biologic process. We know that it is. It is particularly occurring
in the developing organism. And I want to emphasize that
the developmental years are not just the fetus, which is what
we thought early in this field, but in fact it’s all the way
through at least to young adults, certainly including adolescence. And that’s true that susceptibility
is different across that range. But it certainly extends
beyond the very early periods. We call it developmental
programming. It happens without any change
in the inherited genome. And that’s called epigenetics. So it doesn’t change the
structure of the DNA sequence. But it changes the way
genes are expressed. We know that the exposures that
can do this, or known to do this, are nutrients, which is what
we’re going to talk about. But also stress, I know some
of you are interested in that. Stress is a very important one. Oxygen, chemicals, and
toxins in the environment, are another big area of interest in
causing developmental programming. And we are going to talk
more about pathways. So changes in organ structure,
if this is occurring in utero, or in the early-postnatal
period, when organs are still developing their structure. That’s permanent, if it occurs then. There’s change in cell
and organ function. We really don’t know much about
what is and isn’t reversible, in that setting. And there is, very importantly, a
change in the regulatory systems of our body. The systems that respond
to the environment, those are our survival systems. And we’ll talk a lot more
about how that’s changed and why that causes disease. The big-picture point is that when
you have developmental programming, it doesn’t automatically
lead to disease. It depends on what else happens. So, it sets you up
for vulnerability, and that is a positive
note, because we can then begin to understand what are
the factors that will interact, and amplify, and lead to disease. So I want you to know,
just as an aside, that we’re talking about
metabolic syndrome. And these again, are the things
that fall under that heading, a very large list. But there are now, we
know, many other entities which are increased or amplified
risk, by developmental processes. Immunologic, muscular,
skeletal, very importantly mental and behavioral, and
certain kinds of cancer. So, I’m just going to
look at a subset today. Now you have to get
your head in gear, and it actually took
me a number of years to really get this idea in my head. So what I’m showing you
here, is that the nutritional life of the egg, the
human egg, or ovum, is in fact trans-generational. So I’m going to look
at the daughter here. Here’s the daughter as a child. And here she is as a
fetus in mother’s womb. That fetus was derived from
the ovum in mom’s ovary. And that ovum was, in
fact, formed, when mom was a fetus in grandmother’s womb. So if you think
about the forces that could impact on this
individual’s daughter’s health, it really goes all the way
back to the grandmother. And we’ll talk more about that. Now I want to emphasize, if
you don’t live in this field, it can get confusing. So, most of our data, and
what I’ll talk about first, come from the period of the
individual pregnancy itself. OK, what forces are acting here
to cause developmental programming and affect the health? But we will then, a bit later,
come to this earlier period, mom’s lifelong nutritional
exposures up to pregnancy, but before that
pregnancy is initiated. Also play a role in terms of the
status of mom’s body and ability to nurture a fetus. So that we now know,
is also important. So this is the biggest, and
maybe not the biggest picture, but this is an overview. And then we’re going to dive down. So, we are looking
along a life course, from conception all the
way through adulthood. And what we’ve learned is
that the susceptibility to having this developmental
programming occur, is very much dependent
on developmental stage. And it is greatest in utero. OK, so before birth. It’s still very, very prominent
in infancy and childhood. And then, it balloons again
in adolescence, particularly the adolescent brain. And that’s something that’s
really being looked at closely. And we really don’t know
much about adulthood, but we know that at least
certainly some severe exposures can have changes there. Right, so we’re going to
focus down on nutrition. And we’re going to look at
under-nutrition as a programming force, and that can be
from a low-protein diet, or a low-calorie diet, that’s
what’s been specifically studied. But there’s a huge range of
nutritional deficits out there that we haven’t looked at. So it’s very difficult to
know in an individual person. And we know that that
situation causes lower birth weight, and an asymmetric
form of growth restriction, which we’ll talk about. And that leads to vulnerability. In that case, we typically
see rapid childhood growth. And leading, most
commonly, to obesity metabolic syndrome
in adults, at least, and starting in young adults. We also know now, and
we learned this later, as the obesity
epidemic was coming up around us, that high-calorie
malnutrition, which occurs in the situation of maternal
obesity, or maternal high-fat diet, or gestational diabetes,
in those situations provide excess nutrients to
the fetus, or to the child. And from the
intrauterine standpoint, you get higher birth weights, and
a condition called macrosomia. And we’ll talk about that. In this case, you get rapid
infant growth, rather than rapid childhood growth. And again, interestingly, you
get obesity metabolic syndrome. So the two ends of the
spectrum, either one, can give us the same picture. And that tells you, that
something very stereotypic is going on in terms
of the way the body is responding to these
nutritional stresses. Now I want to focus
first on under-nutrition. And give you a little bit of
history about how this developed. This is a slide from
David Barker, this was the very first inkling
that the environment could cause chronic disease. In this case they were looking
at coronary artery disease, and they were looking in
men, in England and Wales, who died from coronary heart disease
in this 10-year block of time. And they saw this
fascinating difference. It was really a socioeconomic
health disparity, in that in the red zones, there
were high levels of coronary deaths. And compare that then to the
green zones, when it was very low. So, no gradations. It was really high and really low. Now David Barker was
Renaissance-educated, and he knew things that
most people don’t know. He knew that the land
was very difficult here. Poor soil, poor food,
and this is where the Industrial Revolution started. So it was a dirty,
polluted, industrial area. In contrast to the green areas,
where it was a very rich soil, and people might not be
rich, but they had good food. So, he asked the genius question. He asked, these men who
were dying in 1968-78, what was happening in
those areas while they were being wombed, while they
were developing in the womb? And to answer that, they
didn’t have longitudinal data, but they went back to neonatal
mortality in those same areas. And what they showed was
an identical pattern. So very high neonatal
mortality in the red zones, and low in the green zones. And that was the clue that
something in the environment was causing coronary
disease in later life. This just gives you a
picture of what was happening in those red areas, smokestacks. These, I have to tell you
this, this is amazing. When I saw these I thought
there were container boxes, these were the housing for
the workers in the factory. So it was a very dire
kind of situation. So David Barker went on, he searched
England, and he searched the world, for databases that
would allow him to have longitudinal data connecting
what happened at birth and what happened in later life. And ultimately, over time,
it was shown worldwide, that if you plot mortality
or any given chronic disease, I’m showing you coronary disease
and stroke, glucose intolerance, hypertension, that if you look at
birth weight, and relative risk of disease, the lower
the birth weight, the higher the risk of disease. And that is really important in
terms of the nutritional health. And they’re using birth weight
as a surrogate for poor growth in the womb, which from
these older cohorts, it was all under-nutrition. So what does under-nutrition do? It causes this asymmetric
form of growth restriction. And this is growth-restricted
baby, compared to a normal baby. They’re thin, because they
lose more weight than height. They tend to protect their height. The fetal blood flow
is redistributed, it goes more to the
heart and the brain, rather than to the lower organs. And so, my favorite organ, and
others below the diaphragm, are in fact more
short-changed in their growth than the heart and the brain. That’s been called
heart-brain sparing, and that gives you a
reduced abdominal girth. And you may see reduced
muscle mass, and therefore low arm circumference. So this pattern is a more
important indicator of poor growth, than just the birth weight. And in fact, in retrospect, we
wonder why the birth weight even served as well as it did. So this pattern can occur
really at any birth weight. There are, as we said, gradients of
susceptibility, and for each organ, in utero. And in early infancy,
there are specific windows. So when the insult occurs,
if it’s a finite one, that will determine the outcome,
depending on which organ, and determine which
organ is affected. And just to show you, for
example, that with the kidney, we know of two important areas,
but it’s all done before birth. And that’s very important. The heart continues a
little bit after birth. But again, that brain
continues throughout, in terms of being susceptible. OK, now I want to talk
to you a little bit about the pathophysiology. And I know this looks daunting. It’s not really, I’ll
take you through it. But I want to emphasize
that both the malnutrition pathways, or exposures, as well
as stress, as well as toxins, they all work through
epigenetic changes. We don’t know very
much about it yet, we don’t know whether to what
degree they’re reversible yet, but that is thought to be a
key point where everything is coming in, stimulating
biologic sensors, and making epigenetic changes. And I’m going to talk about
four different pathways that are activated by the
epigenetic changes. The first one is, if it’s
occurring during organ development, a change in the
organ structure and function. The second one is, an increase
in the stress reactivity systems. These are fundamental
survival systems that occur, that were developed over evolution. This is the hypothalamic
pituitary axis and cortisol, the sympathetic nervous system with
epinephrine and norepinephrine. So that’s a big one. There is an increase
in the reactivity of immune and inflammatory systems. That’s in every disease you look at,
if you’re reading the literature, inflammation comes
up, again and again. So in this programmed state, that
response system is heightened. And then there’s energy
dysregulation, and that one, of course, it’s very important
for our discussions of obesity. We know that all of these
various pathways are activated, very long-lastingly, we
don’t know what’s reversible, and they all feed in to three
mechanisms of tissue injury. The inflammation, as
I suggested, oxidative stress, and insulin resistance. All of them feeding into that. And what you come out with is what
I call, a susceptible phenotype. You’re vulnerable, but it’s a
phenotype, it’s not a genotype. But it’s long-lasting. And then, depending on
what you encounter, later on in the environment. For example, a Western diet
is considered a second hit. It says, if you need
something happening out here, to amplify these processes, and
have you develop outright disease. All right, I’m going
to talk a little bit about the specifics for
altered organ structure and function, for these
hyperactive survival system responses, and then,
show you a little bit, how that interacts post-natally,
and contributes to disease. So, for organ structure, I’m
usually talking about the kidney here, so don’t let me
veer off into the kidney. A number of organs are critical
to metabolic function and energy regulation. And many of you know that. Let me just remind you of that. So this shows a list of
organs, and the deficit that occurs under
developmental under-nutrition. And what we can expect
in terms of an outcome. So, I’m going to look, primarily
at the highlights in yellow here, we know that with the pancreas, the
key functional unit for insulin, is the islet beta cell. And the numbers of
those are decreased. And that means your maximum capacity
for insulin secretion is reduced. That reduces your capacity
to defend against diabetes, particularly if you’re
on a high-sugar diet. Muscle mass is critically important. So we know that that’s
a major determinate of basal metabolic rate,
that means calorie burning. If your muscle mass is reduced, as
with under-nutrition in early life, you have a reduced
basal metabolic rate, it decreases your maximum
exercise capacity. And in animals, it decreases
your interest in moving. We haven’t been able to
confirm that in humans yet. It’s going to be tough. It decreases your
insulin sensitivity. Critically important things
for how you handle energy, and whether or not you’re
at risk for becoming obese. The kidney, see I did it! The liver is critical, with
lipid and glucose metabolism, and the neural circuits are amazing. So in both ends of the
nutrition spectrum, we know that neural circuits
are structurally altered. The ones that are controlling
appetite, and stress reactions, the ones that are controlling
the satiety center. And when our body tells
us that we’ve had enough, that can be impaired. So a range of organs are
influenced, that have impact for metabolic function,
and energy regulation. So now I want to turn to these
hyperactive, survival-system responses and talk about two things. The first is the thrifty
phenotype, and show you how that feeds in to
obesity metabolic syndrome. And a little bit about the stress
system, the cortisol responses that are increased, they’re
hyperactive and cortisol is elevated, following developmental
programming by nutrition. The thrifty phenotype is
one of the many things that David Barker gave us. He published this back
in 2001, as a hypothesis, it’s now been amply confirmed. His idea was that the fetus is
adapting to a nutrient deficit by permanently increasing
energy utilization efficiency. So what is that? That means that in a growing
organism, the amount of energy that you take in, goes to a certain
amount of tissue weight gained. Energy utilization efficiency
means that for a given amount of calories, you
have more weight gain. So those are biologic processes
determining that adaptation. Increase in brain appetite promoting
circuits, we talked about that. That’s been shown now. These permanent adaptations,
according to David’s theory, was that you enhance tolerance
to a sparse nutrient environment. So if you’re born into
the same environment that you were wombed in, if
it’s a low-resource environment, then you’ll be better
able to tolerate that. Now, I question that
from some later data. I don’t think it’s
as simple as that. But it’s easy to remember. Certainly though,
since the same thing happens with excess nutrition,
clearly evolution did not, or has not, yet adapted
us to that, because we’d see the same thrifty phenotype
with high-calorie malnutrition. Some examples, the rural
to urban transition. This was first described
in India, where rural residents, very sparse
diets, thin people, thin animals, massive migration to the cities. Diets in the cities were very
different, much more calories, much more refined carbohydrate and fat. And there is now, and
has been for some years, an epidemic of obesity metabolic
syndrome in the Indian cities. Another example is our US immigrants
coming from the third world. So if they’ve come from
environments of sparse nutrients, often very healthy sparse nutrients,
coming into our environment, and they are at very
high risk of developing obesity metabolic syndrome. And I think I have time to tell
you, I won’t name the company, but I have to tell you another
really terrible example. And that is that
certain food companies, are as a deliberate decision,
marketing in very rural communities in South America and Africa. And they go in with
these little carts that hold all of their sugary products. They identify mothers, in those
rural villages, to be vendors. And they pay them
a tad bit for that. And those mother-vendors go
door-to-door to their neighbors, and sell these products. They educate their neighbors
that these are healthy products, and they are sold at prices
that are less than real food. So, we now are seeing
obesity in both the children and the mothers in that setting. So again, we have a
lot working against us. But we won’t give up. OK, so think about
the thrifty phenotype. So you’ve been altered in your
energy homeostasis, you’re born, you have an increased appetite
that’s biologically embedded. You have this energy efficiency. You may have decreased
locomotor activity. And let’s say you’re exposed
to just regular food, not, you know, even good food. You will have accelerated
growth, because you’re going to eat more relative
to your body weight, than you otherwise would. And you get accelerated
growth, which means that maybe you
started at a 15-percentile, let’s say when you were born,
you’re going to accelerate and you’re going to go
above that percentile. So let’s say you go to 40%. You’re still totally
within the normal limits, but you’ve had rapid growth
with crossing centiles. You may or may not see
obesity accompanying that. And I think that depends
greatly on the diet. You will increase your body
mass to that higher level. And just to emphasize,
people who don’t think in terms of
percentiles or centiles, so when you look at children’s
height and weight, et cetera, you have charts. And they’re showing
you, at a given age, the span of the normal range
of weight, or height, or BMI. So this is the upper
limit of normal, and this is the 10th
or the 90th, and this is the 10th, not an
upper limit, but that’s the 90th percentile,
10th percentile. So if you’re born here, and
you undergo rapid growth, you’re going to go to some
degree above where you were born. And that’s really all that means. OK, now I want to
bring in here what’s happening with your
hyperactive stress systems. Now cortisol does a
lot of metabolic things that are not good when
it’s up on a chronic level. But what I want to
emphasize today, is that cortisol shifts fat
from peripheral subcutaneous locations to central,
visceral locations. So that’s part of this
syndrome, which you’ve been developmentally programmed. We’ll come back to that. So let’s talk about
how these interact when you’re in a postnatal
world, and you’re faced with additional
stressors that are now often referred to as second hits. So let’s say that you have
your energy alteration and you have your stress
hypereactivity with cortisol. And you’re on a Western diet, high
fat, specifically saturated fat, and high sugar. OK, if you’re not paying attention. And you will again,
undergo accelerated growth. But now with all those
calories, and fat, and sugar, you are very likely going
to put on extra fat. And in the presence
of the cortisol, it is more likely to be visceral fat. So you will be starting on your
way to obesity metabolic syndrome in that setting, in a Western diet. And you can also name psychosocial
stresses, would be considered a second hit, in this setting,
that activate these processes and move you in the same direction. Now, just so you know, another
of David Barker’s contributions, was the fact that just
the accelerated growth in the postnatal setting,
is a risk factor. And we know that from many
studies, these are human studies. And just to give
you an example, this is a typical graph
that I can make and you will see, data, the same type of
graph, whether it’s in this case the prevalence of
metabolic syndrome, or obesity, or hypertension. Any of those elements
look like this. And this shows birth weight, so
here’s the lowest birth weight and the highest birth weight. And in this particular
case, these are adults. And this is what
their BMI looked like. Low, middle, and high in adulthood. And you can see that, just
with the birth weight issue, you have an increased risk
of metabolic syndrome, just if you’re born small,
even without changing your centiles growing up. But if you also increase
your BMI tertile, you can see how markedly it goes
up, even with a normal birth weight. And look what happens
with a low birth weight. So these are interacting, and
augmenting, your risk of disease. OK, let’s look at what happens
with high-calorie malnutrition. That’s not a general term, that’s
sort of the Moore Institute’s decision, we’re going to call
it high-calorie malnutrition. I actually like the
term energy excess, because it’s energy excess
to the fetus or the child, that’s the driving force. Again, we know that
occurs in the setting of maternal obesity,
maternal high-fat diet, or gestational diabetes. And we know that it causes
a higher birth weight, and a condition called
macrosomia, at least typically. Now I should, as an aside, tell
you, that in obese pregnancies, there are complications that can
actually cause growth restriction. But looking at the more
typical side of it, we know that this
so-called macrosomia, can occur from these
entities, and recently suggesting that it can occur
just from hyperglycemia. And what we see is excess fat,
we see a certain asymmetry of skeletal proportions, and
we see that rapid infant growth that we talked about earlier. And again, this too can occur
with the normal birth weight, but it’s certainly more apt to occur
at the high birth-weight ranges. And this, to me, is absolutely
dramatic, this study. And it’s dramatic, it’s
from the Generation R Study, and it’s really a birth
mother, pre-birth cohort, and it looks at the percent
of metabolic syndrome. I want to emphasize that
this is a modern cohort. All right? So when we look back in the old
cohorts, there wasn’t any obesity. It just was not a factor
in those early studies. So here we have maternal
pre-pregnancy BMI, low, normal, overweight, or obese. And if you look at the
percentage of metabolic syndrome, not the percentage of just
obesity, or just this or that, a clinical diagnosis
of metabolic syndrome, which it takes at least
three of those entities, and you look at across beginning
with overweight and then obese. And this is in six-year-old
children, six-year-old children. So if you have maternal
obesity, 22.4% of those children had overt, clinically-diagnosed
metabolic syndrome. So that gives you some
sense of the issue, and the things that we need to deal
with in order to interrupt this. Now I’m going to show
you some information that comes from our own
Primate Center, out in Hillsboro, done by Kevin
Grove and his amazing team, who study chronic, high-fat
diets in their monkeys. And these monkeys are kept on the
diet continuously, over years, and they’re obese. They’re also on a high-fat diet. And what they see are, just
for example, in the liver, they see a hepatic lipotoxicity,
because of fat deposition. They see inflammation
and oxidative stress, those key tissue-damaged entities. And they have fatty liver
disease in the neonate. The brain, we’ve been
talking about the brain is affected, in the fetal
brain, there’s inflammation. And again, those neural appetite
circuits and reward centers are altered, in ways that would
promote increased ingestion. And they have some
studies of behaviors that are absolutely dramatic,
and there’s a video that I still wish I had, to show you. But I’ll try to tell you. We know that the monkey offspring
have increased appetite. They have a very intense preference
for high-fat, sweet, salty foods. And I find that really important
to know, again, this is biologic. This isn’t a choice. This is something that’s
being biologically driven. They have accelerated infant growth
rates, just as we said for humans. Early excess fat deposition,
early onset of puberty, another common finding. And they have increased
anxiety in the females, and aggression in the males. So, additional behavioral entities. So then to bring that concept
back to the human setting. We have a study from 2012, again
a modern group, a modern study, where we’re looking at children
of normal weight, overweight, or obese moms, and ADHD score,
and executive function index. Which is the converse
of what it looks like. So a high index means a
low executive function. So what you can see is
not with overweight, but with the obese setting, there’s
a distinct, significant increase in the ADHD score. And there is an increase
in this index, which means reduced executive function. I’m a parent of an
adopted ADHD kid, so I can tell you it changes your
life, it changes your kid’s life. It’s a very important
kind of factor, which changes your resilience. And so I think that’s
something that is really important to keep in mind. And that’s just one example. We do know that maternal
obesity, at least until recently, has been increasing. I show you this slide because it
breaks it down by neighborhood, socioeconomic status. And that is certainly a
major second-hit factor, in terms of risk of disease. And what you see is that at the
highest socioeconomic levels it’s increasing, but
at a much lesser rate than in the poorer neighborhoods. And that’s something that’s been
confirmed in the CDC studies here. At OHSU in 2010, I haven’t been
able to get updated data on this, 40% of the women who
delivered at OHSU, were obese. And this is not about delivery, or
maternal issues, it’s just generic. But in this, the best
I can find recently, the rates of obesity in
whites, 38%, this is women. Forty-six percent of
Mexican-Americans, 57% in African-Americans. So it really is a crisis. OK, we’ve been looking at those
conditions during pregnancy. Just a little bit about the period
prior to onset of a pregnancy, and why that’s important in terms
of the health of future babies. So we know, in the setting
of under-nutrition, that if mom has experienced
under-nutrition in her early life, that her future fetus
will have slower growth, in utero and as a child. And has an increased risk
of hypertension and obesity. Now it’s not huge, and it’s
not as powerful as what it was for mom when she
experienced under-nutrition. But it is carrying into
the next generation. We know that maternal
under-nutrition, just prior to conception, prior to
conception, in the fallopian tube, that mom’s nutrition matters
at that time, as well. And in response to that,
there’s slowed fetal growth and postnatal hypertension. And then there’s some
metabolic features that we don’t know exactly
where they came from in the moms or when they happen,
but they determine her ability to nurture a fetus. So our understanding, just from that
alone, to make healthy pregnancies we can’t just think
about preconception in the OB-GYN definition. Because their definition,
I think the last I heard, was one month before pregnancy. And usually, it’s not
even before pregnancy. And yet, we need to be thinking
about mom’s whole nutritional history, if we want to have healthy
pregnancies for future kids. And I told you earlier that
the high-calorie malnutrition programming is typically associated
with childhood onset of disease, and I showed you some data for that. So let me just have you think
about that at another level. So, here we are, and I’ve
changed my labels here. So now here’s mom,
and she has obesity. And she has a daughter. That daughter has a
very high risk of having obesity as well, especially
if there are no interventions. And because of statistics that
most of you probably know about, we know that if you
have obesity as a child, that you will commonly carry that
into your reproductive years. And we know, now, that that means
that she is likely to be obese when she has her children. And that her children will
likely be programmed by that, and have obesity as children,
et cetera, et cetera, et cetera. So now we’re talking about
risk of obesity passed down across generations, successive
generations, not just one, and keeping the strength of
it, because the strength of it is how mom’s body is at
the time of pregnancy. So I think that is really
our 21st century crisis. And again, it totally
emphasizes the fact that we can’t think about
the pregnancy after it after it’s happened, we can’t
even think about it in a year before it’s happened, but
that’s better than nothing. If we really want a
change, we’re going to have to think about this whole
trans-generational scenario, and we’re going to
have to start making really healthy little kids in
elementary school, middle school, high school, and college. That whole range. We’ve got to change the food
culture, the food knowledge, and change the nutritional
health of those kids. OK, now I have some hopeful facts. I told you we didn’t know much about
whether we can reverse epigenetics, but there’s really powerful data
that cardio-respiratory fitness really does reduce the
cardiovascular risk of obesity, independently of whether
or not you lose weight. I think that’s really
important to know. It’s something you can
state with real confidence, in terms of people who
are struggling with this. It reduces the inflammatory
markers, the abnormal lipids, the insulin sensitivity
increases, muscle mass increases, longevity increases. So that’s a very hopeful thing
that we all need to use, liberally. You’re going to hear
more about healthy diet. So I’m not going to say much,
except that there certainly are elements of healthy
diet that are really going to make a difference, in
terms of cardiovascular risk. And I want to mention
time, strangely. This process, this multisystem
metabolic dysfunction, it’s a process that
occurs over time. So that gives us the
opportunity to intervene. That also gives individuals
the opportunity, you know, OK, you may
be overweight or obese, but you haven’t had it all
your life, make changes now. And it will make a difference. So I think that’s another message
that we really need to emphasize. This just is some
of the data, looking at the cardio-respiratory fitness. This is just a series of
studies and this, over here, favors high mortality. This is the obese
individuals who were not fit. And this was using specific
cardio-respiratory assessments. You can’t just decide
whether or not you’re fit, there are some specific definitions. But you can see that those
that were unfit, on the whole, had an increased
cardiovascular risk. But looking at obese individuals who
were fit, that was, in most cases, reduced to near-normal. So it is something we
really want to think about. I think we talked about that. OK, so this is things you know. Healthy food choices
for that whole range. And this says women, but
it needs to be everybody. I didn’t talk about dads. We’re learning more
about dad’s role in this. They’re not typically as
dramatic as the role for women, but they’re going to be really
important in toxic exposures, because of the sensitivity
of sperm to toxic exposures. So we’re actively
learning about that. I thought I had one more slide that
I was going to show you and I guess I didn’t. So, thank you. [APPLAUSE] Moore Institute thanks you. [APPLAUSE] And I’ll take questions. DEB: Thank you, Susan. We appreciate it. And we’re going to take some
time now for some questions. I’d like to open it
up to the floor, here. And then we’ll take a few from
our online participants, too. Is there anyone here
who would like to get us started with a question, comment? Come on over. The microphone is for the recording. And you will all have access
to this session recorded. If you need to get a
little volume boost, we’ll be able to do that too. AUDIENCE: I think,
looking at global health and the thrifty phenotype is
really interesting to me, because of the fact that as we’ve
transitioned away from having people die from starvation. And so we’ve had an increase
of food availability, but if food availability
is also increasing obesity, based on the thrifty
phenotype, how are we thinking long term
about how to maybe change that negative programming? Or is there any research looking
at that from a global perspective? SUSAN BAGBY: OK, from
a global perspective, I have to tell you that
developmental origins research, started outside the United States. And there are major centers
in India, for example, in South America. So there is awareness there. And I would also, before
answering your question, point out, that there’s still
a pretty high rate of births, for example, that are afflicted
by some aspect of under-nutrition. Be it prematurity, or small
for gestational age, et cetera. So we’re not past that. And I think everybody
is really trying to find interventions
that work, but of course since both of those limbs,
in terms of the exposures, can cause obesity metabolic
syndrome, you have to, sort of, take them all into account. Can we change the food
culture of the world? I don’t know. I hope we can change it in the
United States and then expand. The Gates Foundation is
very much into this concept. We’ve tried to get their
thinking more focused here, I think eventually we will. They have other priorities like
infectious disease and things that are very important also. So I don’t have a good
answer, but people are looking very hard at that. SPEAKER 1: We have
one online question. What are the epigenetic
effects of men? I know you talked about
this just a moment ago, but is there anything else
that you would want to say? SUSAN BAGBY: OK so in terms of the
epigenetic effects of programming, there are some sex differences. But in general, the
epigenetic changes from these various exposures
affect men and women. So that I can say. Now, if you’re asking about,
say, an exposure in a man, and how that gets to the offspring. The key there, is the only way that
the male, at least that we know of, the only way that the male can
contribute to the offspring traits, is through either the sperm
or the spermatic fluids. And so that’s being
looked at very carefully. We know that toxic
exposures can cause mutation in sperm that can be transmitted. We know that the
older the sperm are, the more spontaneous mutations that
occur that can then be transmitted. There are other
mechanisms that they’re learning in terms of epigenetics in
the sperm, that can be expressed. But again, it’s just in its
infancy, and a long way to go. That’s a great question. DEB: Another question
in this audience? We’ll go to this
side of the room now. AUDIENCE: OK, I was curious about
the increase of energy utilization. When you were talking about how the
fetus adapts to nutrient deficits permanently, and because I’m also
taking cell biology right now I’m wondering, is the
body still generating the same amount of ATP
from nutrient molecules, and then somehow doing more with
the energy than a different body? Or are they actually producing
more ATP molecules out of each nutrient input? SUSAN BAGBY: That’s
a great question. It’s a great question no
matter how you look at it. One thing you should
know, is that one of the areas that’s being looked
at very closely is mitochondria. There’s actually some evidence,
and these are from animal studies, that the ovum before pregnancy,
while it’s still an ovum, can undergo mitochondrial damage
before the pregnancy even occurs. And that mitochondrial
change can be transmitted. And it’s shown up like in
skeletal muscle, and liver, in the offspring. So mitochondria are a
real focal point in terms of understanding how this works. But I would love to know the answer
as to how they handle the energy. There is evidence, again
this is animal data, that the changes in
energy metabolism, are very long-lived,
if not permanent. And that comes from evidence, and
it goes back to the US immigrants coming in and being
at increased risk. There is evidence,
in an animal study, that you can go 50
generations of exposure to a low-calorie diet,
or a low-protein diet, and then change to a
normal diet, and they took it down two generations,
and that that energy efficiency persisted. Now that’s animals. We don’t have the
data in humans, but it would suggest what we know
in humans, is that it also may be very long-lived. Thanks for the question. Great question. SPEAKER 2: So the
next online question was, if you have
gestational diabetes and have a high birth weight infant,
but mom is healthy otherwise, does that give the infant
the same risk for obesity as the mom with over-nutrition? SUSAN BAGBY: So in the setting
of maternal gestational diabetes? Yes, that is considered
one of the conditions which provides excess nutrients,
excess energy, to the fetus. And does cause the same thing, as we
understand it, as maternal obesity. There are going to be some
tweaks and differences, but overall, it does
carry an increased risk. It is not an absolute. But I would tell somebody
who was in that situation, is you want to be
aware of that risk, and be very particular
about training your child’s preferences occur very early, about
modulating those toward a really healthy diet, and not sugar,
and not saturated fat, and just take all the steps we know
you can take to minimize that risk. And the other would
be, build in exercise. Good question. DEB: Another question here
in the audience, right here. AUDIENCE: Yeah, I was
wondering with this research, would you say that eating disorders
can be passed down biologically from the mother? SUSAN BAGBY: I don’t know. And maybe, do you guys know? Yeah I don’t know, I
was trying to think, I guess you’d have to
define your eating disorder. AUDIENCE: Well if
someone is bulimic, or is eating an
excessive amount of food, and then with a
period of restriction, does that affect your
biology in the same way that you’re saying
malnutrition, in a sense? SUSAN BAGBY: It’s a great question. I don’t know the answer to that. I would think that if it did express
itself in an eating disorder, it would be bulimia. Or the over-eating end of things,
from what we know from programming. And I would also think,
when is this happening? Is this happening in an adolescent? Or is it happening in a child? If it hasn’t been
there during childhood, and it appears as an adolescent,
I would think look at that differently. That’s probably not programming. But I do not know, and
it’s a great question. SPEAKER 3: What percentage does
the weight-height ratio need to be, for the infant to be classified
as thin from under-nutrition during pregnancy? SUSAN BAGBY: I am sure
there is data on that. But I do not know that. I would look it up online in the
OB-GYN literature, specifically the obstetric literature. I’m sure it’s available,
I just don’t know that. DEB: We have another
minute so who else? I’ll try to get back there too. AUDIENCE: Thank you, I was curious
about maybe the type of birth, like a c-section
versus a natural birth. Would there be any impact
of that on this topic? SUSAN BAGBY: OK that
is a great question. I have some information on that. It turns out that one
of the important things, and I didn’t mention this,
in terms of our metabolism, is our gut microbiome. And we’ve learned that a
baby with a vaginal delivery, picks up bacteria
from the birth canal. And that’s part of what sets up
the babies, not only their gut, but other aspects of their
body, in terms of microbiome. And we also know that in cesarean
section, that doesn’t happen. And I don’t know a lot of
detail, I can’t tell you much about what the differences are. But I wouldn’t be
surprised if down the line, we’ve gotten so free with
probiotics, and pre-biotics, that we’ll be making some effort
to replace that in the future. But as far as I know,
that’s not happening yet. It’s a great question. It’s important. And there may be other
things, because everything seems to be sensed by the fetus. So that sensing of pressure,
what is that doing? All sorts of questions
that go along with that. Thank you. DEB: I’d like to thank
Susan Bagby again. [APPLAUSE] Thank you very much, we
really appreciate it. [APPLAUSE]

One thought on ““The Science of Obesity: Fighting Fat with Fact” presented by Dr. Susan Bagby

  • I’ve had my thyroid removed 2011, and it’s been a struggle to lose weight. Will this program address those without a thyroid?

Leave a Reply

Leave a Reply

Your email address will not be published. Required fields are marked *