Dr. Ted Naiman - 'Insulin Resistance'
Summary
TLDRThe speaker emphasizes the critical role of insulin resistance in chronic diseases, highlighting the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) as a key metric. They explain how abdominal fat and adipocyte size contribute to insulin resistance and the development of diseases like diabetes and cardiovascular conditions. The talk delves into the impact of diet, particularly glucose intake, on fat storage and mitochondrial function, advocating for a shift towards a lower carbohydrate diet to improve metabolic health and flexibility.
Takeaways
- đ Chronic diseases like cancer, cardiovascular disease, and neurodegenerative diseases are largely driven by sedentary lifestyles and malnutrition, underpinned by insulin resistance.
- đ The Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) is a non-invasive method to measure insulin resistance and is commonly used in medical literature.
- đ A high percentage of deaths due to chronic diseases are associated with insulin resistance, as indicated by a high correlation between HOMA-IR and various chronic conditions.
- đ Insulin resistance is linked to the size of adipocytes (fat cells); larger adipocytes are more resistant to insulin and contribute to metabolic issues.
- đ Gastric bypass surgery can shrink adipocyte size, which can reverse insulin resistance and diabetes, emphasizing the importance of adipocyte size over total weight loss.
- đœïž Consuming a diet high in carbohydrates leads to increased fat storage as the body prioritizes glucose metabolism over fat oxidation, contributing to obesity and insulin resistance.
- đ Metabolic flexibility, the ability to switch between burning glucose and fat, is crucial for maintaining metabolic health and is often impaired in individuals with obesity and insulin resistance.
- đ« Glucose and fat are oxidized reciprocally in the body; an excess of glucose inhibits fat oxidation, leading to fat accumulation and insulin resistance.
- đ± The modern diet, high in sugars and fats, is similar to obesogenic rat chow, promoting rapid weight gain and metabolic issues.
- đ Natural bodybuilders and fitness models achieve low body fat by following a high-protein, low-carb, and moderate-fat diet, which supports smaller adipocyte size and lower insulin levels.
- đĄïž The constant availability of high-calorie, processed foods has made it 'always summer' for our bodies, leading to overfilled adipose tissue and widespread insulin resistance.
Q & A
What is the primary focus of the talk?
-The primary focus of the talk is on insulin resistance, its causes, and its impact on chronic diseases such as cancer, cardiovascular disease, and neurodegenerative diseases like Alzheimer's.
What is HOMA-IR, and how is it used?
-HOMA-IR (Homeostatic Model Assessment of Insulin Resistance) is a method to non-invasively measure insulin resistance. It is calculated using fasting glucose and fasting insulin levels and is used to assess how much insulin is required to maintain blood sugar levels.
What are the 'five buckets of death' mentioned in the talk?
-The 'five buckets of death' categorize the causes of death into five groups: toxic, kinetic, microbial, genetic, and chronic diseases. Chronic diseases, which include cancer, cardiovascular disease, and neurodegenerative diseases, account for about 70% of all deaths.
How does abdominal fat relate to insulin resistance?
-The more abdominal fat a person has, the more insulin resistant they are. Insulin resistance is driven by factors like sedentary behavior and poor diet, leading to the accumulation of abdominal fat.
Why do some people with a low BMI still have poor insulin sensitivity?
-Some people with a low BMI have poor insulin sensitivity because of the size of their adipocytes (fat cells). Larger adipocytes are more insulin resistant, regardless of overall body fat or BMI.
What is the significance of adipocyte hypertrophy and hyperplasia?
-Adipocyte hypertrophy refers to fat cells becoming overstuffed and inflamed, leading to insulin resistance. Hyperplasia refers to the creation of new, small fat cells that remain insulin sensitive. People with hyperplasia can stay insulin sensitive despite having more fat.
What is the 'personal fat threshold' (PFT)?
-The 'personal fat threshold' is the genetic limit to how much fat a person can store before becoming insulin resistant. Once this threshold is reached, fat starts to accumulate in other tissues, leading to insulin resistance and metabolic issues.
How does mitochondrial function affect insulin resistance?
-Defects in mitochondrial function impair the ability to burn fat, leading to fat accumulation and insulin resistance. Proper mitochondrial function is essential for maintaining metabolic health and preventing insulin resistance.
What role does metabolic flexibility play in insulin resistance?
-Metabolic flexibility refers to the ability to switch between burning fat and glucose efficiently. People with poor metabolic flexibility struggle to burn fat when needed, leading to fat accumulation and insulin resistance.
How does the combination of high fat and high carbohydrate intake affect insulin resistance?
-A diet high in both fat and carbohydrates leads to the highest insulin levels, most overfilled adipocytes, and worst body composition, driving insulin resistance and metabolic issues.
Outlines
đ Insulin Resistance and Chronic Disease
The speaker opens with gratitude towards Iver and humorously acknowledges that his talk might be repetitive for those who have heard similar topics before. He delves into the significance of insulin resistance in chronic diseases, referencing Greg Glassman's 'five buckets of death' and emphasizing that 70% of deaths are due to chronic diseases driven by sedentation and malnutrition. The Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) is introduced as a method to measure insulin resistance non-invasively, with an average value of 1.75 considered high. The speaker connects high HOMA-IR values with various chronic diseases and all-cause mortality, highlighting the importance of addressing insulin resistance.
đ Causes of Insulin Resistance
This paragraph explores the causes of insulin resistance, starting with the correlation between abdominal fat and insulin resistance. The speaker discusses how the size of adipocytes (fat cells) is directly proportional to insulin resistance, explaining that larger fat cells are more resistant to insulin's effects. The concept of adipocyte hypertrophy versus hyperplasia is introduced, noting that having more small, insulin-sensitive fat cells can prevent insulin resistance despite a high BMI. The speaker also touches on the idea of a 'personal fat threshold' (PFT), which is a genetic limit to how much fat one can accumulate before becoming insulin resistant.
đ Adipose Tissue and Insulin Resistance
The speaker discusses the role of adipose tissue in controlling insulin resistance, using the example of lipodystrophy to illustrate the point. Lipodystrophy is a condition where individuals lack subcutaneous fat, leading to high levels of visceral fat and severe insulin resistance. A study on lipodystrophy mice, where subcutaneous fat was surgically implanted, showed a significant reduction in insulin resistance. The speaker also mentions Glitter zones, a class of diabetes drugs that increase body fat and slightly improve insulin resistance, but are not favored due to their mechanism of action.
đ Metabolic Flexibility and Fat Oxidation
The paragraph delves into the concept of metabolic flexibility, which is the ability to switch between burning glucose and fat based on availability. The speaker explains that a high respiratory quotient (RQ) indicates a preference for burning glucose over fat, which is associated with higher body fat and insulin resistance. The importance of mitochondria in fat oxidation is highlighted, along with the idea that defects in mitochondrial metabolism contribute to obesity and insulin resistance. The speaker also discusses how a diet high in carbohydrates can lead to reduced fat oxidation and increased fat storage.
đ« Glucose Control and Mitochondrial Dysfunction
This section focuses on how glucose controls metabolism and substrate oxidation. The speaker explains that the presence of glucose in the body leads to increased citrate production, which in turn inhibits the entry of fatty acids into the mitochondria, preventing fat oxidation. This process is described as glucose toxicity, where excessive glucose can damage mitochondria and impair their ability to oxidize fat. The concept of glucose hysteresis is introduced, which refers to the inertia in metabolism that makes it difficult to switch from a high-carb to a low-carb diet.
đŹ The Impact of Diet on Insulin Resistance
The speaker concludes by discussing the impact of diet on insulin resistance, drawing parallels between the obesogenic rat chow and the standard American diet, which is high in sugars and fats but low in protein and nutrients. The paragraph emphasizes that consuming a diet high in carbohydrates and fats leads to overfilled adipocytes and high insulin levels, contributing to obesity and insulin resistance. Conversely, a diet high in protein, low in carbohydrates, and moderate in fat, combined with resistance training, can result in smaller adipocytes and lower insulin levels, promoting metabolic health.
Mindmap
Keywords
đĄInsulin Resistance
đĄHomeostatic Model Assessment of Insulin Resistance (HOMA-IR)
đĄAdipose Tissue
đĄEctopic Fat
đĄMetabolic Syndrome
đĄPersonal Fat Threshold (PFT)
đĄLipodystrophy
đĄMitochondrial Dysfunction
đĄMetabolic Flexibility
đĄRespiratory Quotient (RQ)
đĄGlucose Toxicity
Highlights
Insulin resistance is a significant driver of chronic diseases like cancer, cardiovascular disease, and neurodegenerative diseases such as Alzheimer's.
Homeostatic model assessment of insulin resistance (HOMA-IR) is a non-invasive method to measure insulin resistance commonly used in medical literature.
Higher HOMA-IR values are associated with a greater risk of chronic diseases and all-cause mortality.
Abdominal fat is strongly linked to insulin resistance, but not all fat distribution is equal in its impact.
Adipose cells' size, not just quantity, affects insulin sensitivity, with larger adipocytes being more resistant.
Gastric bypass surgery can reverse insulin resistance by shrinking adipocyte size, emphasizing the importance of cell size in metabolic health.
Adipose tissue expansion has a limit, beyond which insulin resistance occurs, known as the personal fat threshold (PFT).
Ectopic fat, or fat stored in non-adipose tissues, contributes to insulin resistance and is a sign of metabolic dysfunction.
Lipodystrophy, a condition with little subcutaneous fat and increased visceral fat, is a powerful example of adipose tissue's control over insulin resistance.
Mitochondrial dysfunction is implicated in the impaired ability to oxidize fat, contributing to obesity and insulin resistance.
Respiratory quotient (RQ) is a measure of an individual's metabolic flexibility and their tendency to burn fat or glucose.
A high RQ indicates a preference for glucose oxidation over fat, which is associated with increased body fat and insulin resistance.
Glucose and fat oxidation are reciprocal processes at the mitochondrial level, with glucose inhibiting fat oxidation.
Glucose toxicity in mitochondria can occur when excess glucose leads to overdrive of the electron transport chain and reactive oxygen species production.
Obesogenic diets high in refined carbohydrates and fats are similar to the diets used to induce obesity in laboratory animals.
High-protein, low-carb diets with resistance training can reduce body fat and improve insulin sensitivity.
The shift in American diet towards grains, oils, and sugars has contributed to the obesity epidemic.
Seasonal changes in diet affect adipose tissue expansion and contraction, with modern diets disrupting natural metabolic cycles.
The constant availability of sugars and fats in modern diets has led to chronic overfilling of adipose cells and widespread insulin resistance.
Transcripts
all right thanks everybody first of all
I want to thank Iver for such a great
talk that was awesome my love I've ergh
okay
love you bro Iver just gave my whole
talk like slides and everything so
anybody wanted to get some skiing and
that would be a great time but if you
want to hear me beat a dead horse about
insulin then you know here we go
did anyone catch the CrossFit Greg
Glassman talked last year where he
talked about the five buckets of death
it turns out that anytime somebody dies
it could be categorized as one of five
things you've got up in the top right
hand corner thirty percent of deaths
toxic kinetic microbial genetic but down
in this giant seventy percent of all
deaths you've got chronic disease and of
course the big three cancer
cardiovascular disease and chronic
neurodegenerative diseases like
Alzheimer's what we know about all this
chronic disease is that it's driven by
Seddon tation and malnutrition this is
poor diet and lack of exercise and
underpinning all of this stuff is
insulin resistance and that is why this
is such a huge big topic I mean I will
never stop talking about this because
it's really that important I just want
to say at the top of my talk here that I
use home I are a lot in my patients
these days this is homeostatic model
assessment of insulin resistance this is
my favorite way to non-invasively
measure insulin resistance to my
patients this is something you'll see
most commonly in the medical literature
when people are looking at insulin
resistance it's really just your fasting
glucose times your fasting insulin
divided by 405 and it's answering the
question and how much insulin does it
take when I'm fasting to hold my blood
sugar and my fat stores where they're at
right now average in this country is
1.75 that's really a little too high you
want to be a 1.0 or lower anything over
about two and a half is clearly insulin
resistance you could just search the
medical literature for Homa IR and any
chronic disease you can think of and
it's just a huge linear Association home
IR and cardiovascular disease huge
linear Association dying of heart
attacks huge association cancer huge
Association all forms of cancer huge
Association I mean it's just ridiculous
Alzheimer's pathology massive
association with insulin
and finally just dying all cause
mortality and home I are big association
there too so this is a really important
topic okay so now what causes insulin
resistance well we've known forever that
the more abdominal fat you have the more
insulin resistance you are this graph on
the right shows insulin levels you've
got normal in green obese and yellow and
abdominal obesity in red so we've known
that for a long time right but what
about this here's a graph of insulin
sensitivity versus body mass index and
how do you explain these people way down
here they've got a BMI less than 20 but
their insulin sensitivity is terrible
and what's going on here right well
we've known for over 50 years that the
larger you're out of a site the more
insulin resistant you are right and in
fact it's a perfectly linear Association
you're out of the site's can expand in
diameter about 20 times so if you look
at a cross-section of out besides in our
microscope they can go from maybe 10 20
microns to 200 microns that means their
volume can expand by eight thousand
times and as they get bigger they get
more insulin resistant and it's very
very linear um it turns out that large
outsides are resistant to the antibiotic
effects of insulin and it's harder to
shove more fat in there right you can
graph out fasting insulin homo IR any
marker metabolic syndrome it's perfectly
linear without up sight-size
triglycerides go up HDL goes down home
IR goes up tinsel in goes up any
metabolic syndrome or insulin resistance
marker you measure will completely
correlate up or down linearly with the
size of your adipocytes if you have
gastric bypass surgery and you manage to
shrink the size of your ateb sites
you'll reverse insulin resistance and
diabetes if you lose weight with any
mechanism it's more important how much
you shrink your adipocytes rather than
how much weight you actually lose in
terms of reversing insulin resistance
and that's why people can reverse
insulin resistance really rapidly even
before they lose a whole lot of weight
it turns out that as you get fatter your
fat cells can do one of two things you
can have adipocyte hypertrophy and
that's where your fat cell gets
overstuffed with fat and it's inflamed
and it's insulin resistant and it
doesn't want anymore fat or
or you can have out of the site
hyperplasia if you have the right
genetics you can sprout cute new little
baby fat cells that are very insulin
sensitive and they're happy to suck up
more fat and they're not inflamed and
they're not insulin resistant so not all
your fat cells are are like great your
ginormous huge overstuffed fat cells are
super inflamed they're sick they're
dying they're spewing out fat constantly
it takes a crap-ton of insulin just
shove fat in there
the fat doesn't want to stay in there
but your cute little baby fat cells are
very insulin sensitive and they're more
than happy to suck up more fat slugs
right so you can have two people of
identical obesity and the person who's
overstuffed their fat cells and had AB
side hypertrophy is going to be inflamed
and insulin resistant and it takes a ton
of insulin to shove anymore fat in there
and the fat is constantly spilling back
out but somebody you can sprout new
little baby fat cells is going to stay
insulin sensitive forever if you have
the right genetics and you can just
sprout new fat cells this hyperplasia
you could be 600 pounds and as long as
you have some small fat cells around you
still suck up more fat you're going to
be totally insulin sensitive this is
about 10% of obese people so there's
this concept of limit of adipose tissue
expansion basically there's a limit to
how easily you can get fatter either by
sprouting new baby fat cells or
expanding the ones you've got and once
you've hit this limit your insulin
resistant so fat is typically stored in
the subcutaneous first and then it
spills over into visceral and then it
spills over into liver and muscle and
pancreas and blood vessels and you've
got ectopic fat you know fat everywhere
and then you're horribly insulin
resistant here's a sort of a schematic
of how it works you still have your
SubGenius adipose first it spills over
into the visceral that spills over into
liver and muscle and now you've got
ectopic fat and none of your tissues
want any fat or glucose and now your
insulin resistant my favorite term when
it comes to this concept is personal fat
threshold PFT this is a genetic limit to
how fat you can get before you just
can't get fatter and your insulin
resistance this explains people who are
Toph I thin on the outside but on the
inside I think dr. Berger mentioned that
and these are people who look thin but
they completely maxed out there
for subcutaneous and visceral and
they're horribly insulin resistance or
maybe completely diabetic this is why
China and India has passed up diabetes
prevalence compared to the u.s. at a
much lower body mass index right
Personals a threshold on this slide it's
just here to remind me that your giant
overstuffed hypertrophy fat cells are
literally dying these gray things on the
right are dead adipocytes and that's why
you have so many macrophages though
these cells are not happy they're sick
they're dying they're inflamed the
little baby fat cells are happiest clams
I love this graph right here it takes a
ton of insulin to shove that much fat
into an adverse it-- and hold it there
and to pin it there chronically and that
fat is constantly trying to speed back
out and that's why people have maxed out
their fat cells just have high insulin
24/7 this is a beautiful illustration
okay the best example we have of adipose
tissue controlling insulin resistance is
lipodystrophy lipodystrophy is a series
of disorders where you don't have any
subcutaneous fat or hardly any I have a
bunch of patients with lipodystrophy
there they're very unique they have they
almost look ripped like like a
bodybuilder they have very defined arms
and legs as very little subcutaneous fat
but they have a lot more visceral fat
than you would expect if you do
cross-sectional imaging on these people
the sub-q fat in red here is very very
small but the visceral fat is completely
maxed out and almost everyone with
lipodystrophy has horrible insulin
resistance and horrible brittle diabetic
diets all of my lab industry patients
really bad diabetes it's the worst
insulin resistance um now you can buy a
mouse that has Lipa dystrophy right we
found mice that lack subcutaneous fat
for whatever reason and we've bred them
and you can actually buy and sell
lipodystrophy mice and it's a great
model for insulin resistance and
diabetes because no matter what you feed
them they just completely max out so
cute a nice fat it all goes to this real
fat they have fatty liver they have
visceral fat their insulin resistant
diabetic just like the humans and we did
this amazing study on these
lipodystrophy mice where we literally
surgically implanted little pouches of
subcutaneous fat under their skin and
connected to blood supply and you
instantly magically cure insulin
resistance in these mice look at this
black line on top here that's the sham
surgery and you're looking at insulin
levels versus fat transplant surgery on
the bottom in white you literally
instantly magically cheer insulin
resistance in these mice by just
implanting sub-q fat in the skin this is
kind of the final nail in the coffin of
anyone who doesn't buy into the theory
that adipose controls insulin resistance
right we haven't done this exact study
in humans I don't think people would
really like that but we do have glitter
zones glitter zone in this class of
diabetes drug that enables you to get a
little bit fatter and it they don't work
that grade that you get a little fatter
and your insulin resistance and diabetes
gets a little bit better I don't like
that if patients knew how it worked they
probably wouldn't want to take it okay
so here's how it works so far right you
fill up your subcutaneous fat then it
spills over to visceral that spills over
into liver and muscle now you've got a
copic fat you've got five everywhere
none of your cells want fat none of your
tissues one side your insulin resistant
what's really going on here is your body
is at war with itself right none of your
cells want fat none of your tissues want
that none of them want glucose either
none of them want any of this energy and
it's like this horrible game of musical
chairs where insulin just gets louder
and louder and louder until you finally
shove some fat or glucose into whatever
cell or tissue is the least insulin
resistant and next time it'll probably
be even more insulin resistant and once
your body is at war with itself like
this the wheels just fall off your wagon
and this is why all of these chronic
diseases are driven by insulin
resistance okay bottom line so far your
insulin resistant because you filled up
all your adipocytes right you have no
more room for fat flux every time you
eat a meal it has nowhere to go the fat
or the glucose so you're just completely
filled and that's why your insulin
resistant and that's why your
hyperinsulinemic and you have high
insulin all the time but that's just
this is just the beginning I mean the
big question is why did you fill up
you're out of sights right why are they
all full is it because humans shouldn't
eat fat because we're should be low fat
vegan is it because you're just a
glutton then you eat too much right No
you filled up your fat cells with fat
because you suck at burning fat because
you eat too much glucose an important
rating factor for obesity is reduced fat
oxidation increase metabolism
carbohydrate this is then brought about
by shift towards the body's preference
for the oxidizing carbohydrate rather
than fat resulting an increased
deposition of body fat you're eating
carbs and glucose you're not burning fat
it accumulates you fill up your adipose
turns out everybody with obesity insulin
resistance ectopic fat has defects in
mitochondrial metabolism of fat everyone
in this situation has trouble
metabolizing fat in the mitochondria
obesity insulin resistance type 2
diabetes and aging all associated with
impaired skeletal muscle oxidation
capacity reduce mitochondrial content
and lower rates of oxidative
phosphorylation basically you're not
burning fat in your mitochondria
mitochondrial now structure function are
altered in insulin resistance defects of
mitochondria are believed to contribute
to impaired fat oxidation and to the
accumulation of intracellular lipid
intermediates which contribute to the
pathogenesis of insulin resistance
mitochondrial dysfunction the elderly
and in the offspring of diabetic
patients is well documented so basically
you're not burning fat well it
accumulates you fill up your adipose now
only your mitochondria can oxidize fat
right it's all happening the
mitochondria and let's talk about them
for a second every nucleated cell in
your body has mitochondria in it right
and they're just constantly turning your
food into ATP which drives everything in
your body and the turnover rate is just
enormous every single day you make your
entire body mass in ATP molecules if
you're a 70 kilogram male you
manufacture 70 kilograms of ATP
molecules every day which is ridiculous
the the turnover is so fast that at any
given second in time you only have six
seconds of ATP left in your body or in
fact that is what on cyanide does
cyanide poisons your electron transport
chain and you can't make ATP in your
dead six seconds later
so these suckers are constantly
performing metabolism and there are
three things going into the cell that
your mitochondria can burn glucose FFA
is free fatty acid dutchess fat or amino
acid
now amino-acids is sort of a minor
player most of the time people are
oxidizing glucose or fat and glucose and
fat are oxidized reciprocally so anytime
you're bringing more glucose you're
burning less fat and more fat you're
burning less glucose right now you can
actually tell what the fuel mixture is
in every mitochondria and every cell of
your body by measuring a respiratory
quotient right you actually breathe out
a lot more carbon dioxide if you're
burning glucose in your mitochondria
then if you're burning fat you breathe
out less carbon dioxide and because
they're reciprocal you can actually
calculate it out if you have a highest
respiratory quotient of 1.0 you're
breathing out the most carbon dioxide
and you're burning pure glucose in all
yourselves all your mitochondria if you
have the lowest respiratory quotient of
0.7
you're burning pure fat when you're
making the least carbon dioxide and
because it's reciprocal you can just
look at that line and tell exactly what
you're feeling extra is based on your
respiratory pollution the fascinating
thing about respiratory quotient is you
could take two people in this room and
measure their baseline respiratory
quotient and whoever has the higher one
meaning they're burning more glucose and
less fat at baseline will literally be
significantly fatter three years down
the road that's what this study was
measured based on our cue whoever is
burning more glucose and less fat is
literally going to be sadder later
defective fat oxidation remains the
likely explanation for this point yeah I
couldn't agree more it turns out you can
take two people of the same obesity
whoever has the higher or whoever has
the lower respiratory quotient meaning
they're burning more fat is going to be
metabolically healthier they're going to
have lower insulin let's metabolic
syndrome if your insulin resistant you
have a hierarchy if you're diabetic you
have a hierarchy if you're obese you
have a higher RQ if you have family
members with diabetes you have a
hierarchy anything bad metabolically you
have a higher R Q and that's just not
good there's also this concept of
metabolic flexibility metabolic
flexibility is the ability to drop your
RQ if you're eating more fat so if I'm
thin and healthy and I have tons of
really good mitochondria and I'm good it
brings out if I eat a high fat diet I
will immediately drop my
our cue and burn more fat also if I'm
fasting and I'm just living off of fat
my RQ goes way down people with poor
metabolic flexibility can't do that they
if they eat a higher fat diet they end
up just storing that if they if they are
fasting they have a struggle to meet
their metabolic needs just from that you
can draw a graph of metabolic
flexibility and insulin sensitivity and
it's just a straight line right now okay
this is a really important point if
you're on a mixed diet and you eat a
bunch more carbs you will immediately
raise your RQ in anybody you can drive
up anyone's RQ by feeding them more
carbs and glucose because glucose
completely controls metabolism and
substrate oxidation it has to because
you don't have anywhere for that glucose
to go so if I feed anyone more carbs
there are Q goes up the same isn't true
on a mixed diet if you're eating just a
regular standard American diet and you
add more fat to it you just throw stick
of butter on top you will not drop your
RQ you'll just store all that butter I'm
reading in this box here excess
carbohydrate results in increased
carbohydrate oxidation a lower fat
oxidation increased our - this is not
the case for fat excess fat intake on a
mixed diet does not stimulate cell
oxidation but enhance its fat storage um
that's because glucose rather than fat
completely controls substrate oxidation
right glucose control oxidation and
here's why
glucose has to control metabolism and
substrate choice professor flat drew
this diagram this hydraulic mechanical
model of metabolism like 60 years ago
and you've got this giant fat reservoir
over here on the right that's 200 times
bigger than this tiny little glucose
carbohydrate reservoir so when I dump a
bunch of fat into the system nothing has
to change I don't have to change my fuel
mixture I can do that all day long on
the other hand you only have a tiny
little carb glucose reservoir it's it's
really small you know you can have what
5 grams of glucose in your bloodstream
maybe a couple hundred grams and your
liver and your muscle and that's it so
when you dump in a bunch of carbs in
blue coats you literally have to switch
your metabolism over and burn more
glucose I've made a fancier little
hydraulic model of metabolism
here and again you've got a fat
reservoir on the right so when you dump
more fat in nothing has to change but as
you add carbohydrates and raise glucose
you literally have to switch your
metabolism over and burn more glucose
just to get rid of it you just have no
other choice that's how it has to work
in fact if you need enough carbohydrates
in glucose you literally have to convert
it to fat via de novo lipogenesis to
store it and get rid of it only when
carbohydrates and glucose are absent can
you switch your fuel mixture over and
burn fat again there's another concept
here and that's glucose hysteresis
there's an inertia to your metabolism a
general feature of metabolic regulation
is that substrate typically induce the
metabolic machinery necessary for their
own metabolism what does that mean if
you're good at burning fat you have
epigenetic changes that up regulate your
fat burning pathways and you'll stay
good at burning fat for a period of time
it's like an inertia to your memory to
your metabolism on the other hand if
you're a glucose burner you operate you
have epigenetic changes you have to
regulate glucose burning and you sort of
stay good at that that's why it takes
you know one to three weeks to switch
over from a high carb diet to a low carb
diet ok this this study sums it up so
well I'm just going to quote directly
from it the development of insulin
resistance is the impaired ability of
skeletal muscle to oxidize fatty acids
as the consequence of the elevated
glucose oxidation and the situation of
hyperglycemia hyperinsulinemia
and the impaired ability to switch
easily between glucose and fat oxidation
and response to homeostatic signals the
decreased out oxidation results in the
accumulation of intermediates of fatty
acid metabolism glucose around you can't
burn fat the fat accumulates now your
insulin resistance this concept of
metabolic flexibility goes all the way
down to the mitochondrial level so
here's your mitochondria with the two
inputs glucose and fat and a healthy
mitochondria can easily flex back and
forth glucose fat glucose set but if you
have an inflexible mitochondria you're
one of these damaged mitochondria it's
really bad at doing that it really
struggles what's going on inside your
mitochondria as you've got glucose and
long-chain fatty acids the to input into
the cell right glucose inside glucose
goes into the mitochondria and when you
dump in a bunch of extra glucose
you have increased citrate and citrate
gets exported to the cell and because
there's extra citrate your body knows
it's time to make fat instead of burning
fat so you're still going to make that
it converts it into melon Alcoa that
literally blocks carnitine pummelled
transfers one CPD one and fat actually
physically cannot enter your
mitochondria to be burned when melon
Alcoa is elevated in other words when
you're making fat you don't want to burn
fat that would be wasteful so all your
fat gets rerouted as triglycerides to be
stored I'm reading the caption here
mechanism of inhibition of fatty acid
oxidation by glucose basically melon
okole inhibits the entry of long-chain
fatty acids into the mitochondria this
effect reroutes fatty acids toward the
certification so when there's a bunch of
glucose present you can't burn fat
here's another illustration the same
thing you dump in a bunch of glucose you
export citrate melon elko a first
committed step to making fat so you
don't want to burn fat and you block
entry of fat into the mitochondria and
all your fat accumulates as
triglycerides to be exported and stored
what's really going on here
is your body is way too efficient to
make fat and burn fat at the same time
so when you dump a bunch of glucose into
your cell your body knows it's going to
make fat right fatty acid synthesis and
melon elko is the first committed step
to fatty acid synthesis block cpt 1
because you don't want to be making fat
on one side here on the right and then
burning fat on the other side but just
that would be a futile cycle right that
your body's not going to do that that's
why glucose inside our burn reciprocally
all the way down at your mitochondrial
level because when you're burning
glucose and you're going to be making
fat you don't want to be burning fat
we've proven that this happened here's a
brilliant study that literally proves us
they are measured oxidation of glucose
and fat in the mitochondria baseline
they infuse people with glucose and
insulin and bam immediately glucose
oxidation goes way up fat oxidation goes
way down this is just how it works
this is why if you eat carbs all day
long you're not burning fat any fat at
all rather the intracellular
availability of glucose not fatty acid
is a prime determinant of the substrate
mix ie glucose versus
that is our size for energy in other
words you dump in glucose you literally
have to burn glucose not fat
that's just how the whole system works
here's a cuter picture of it right
insulin binds to the cell up in the
upper left-hand corner the glut for
transporter goes to the service glucose
comes in it's converted to nominal Co a
because you're going to turn it into fat
so that blocks CP t1 so you don't burn
any fat and then all your fat
accumulates there in yellow now what
let's say I eat just a diet of pure
glucose right I'm some crazy low fat
vegan and all I eat is just sugar I'm on
a sugar diet I'm on some sort of kempner
rice diet okay I only glucose but I
don't overeat and I'm careful with
calories
yes I'm blocking entry of fat into the
mitochondria but I don't eat any fat so
fat isn't accumulating I actually won't
gain weight you can eat a diet of pure
sugar and you will not gain weight
you're horribly locked into glucose
dependence so I don't recommend it at
all now if I dump a bunch of butter on
top of that oh yeah well then I'll gain
a thousand pounds right because you're
blocking oxidation of that with all the
glucose and then all the fat accumulates
and next thing you know your insulin
resistant and in fact what happens is
your cell sees what's going on here all
this fat is accumulating and the
accumulated fat shuts off insulin
signaling so the blood floor transfer
goes back inside the cell and your cells
refusing glucose right your cell doesn't
wanting more glucose look at all this
fat that accumulated your cell doesn't
want glucose right your cells
smarter than you are what could you do
with your diet when your cell doesn't
want more glucose I can't think of
anything but that's probably something
now if we take it even one layer deeper
and look at the electron transport chain
which we saw earlier thanks to dr. Eid
electron transport rates so you've got
you know you're pumping all these
protons across this membrane it's like a
little battery that powers your ATP
synthase motor and it spring loads all
your ATP molecules bla bla bla when
you're just doing beta oxidation of fat
everything runs really smoothly your
level loading your electron transport
chain the membrane potential is perfect
everything's nice your body is designed
to just live off of stored body fat so
just burning fat has to be worked
perfectly but you dumped a bunch of
glucose on top of this and you overdrive
plus one and you get too much membrane
potential in too many reactive oxygen
species and you literally get something
called glucose toxicity in your
mitochondria you can basically bust
those suckers by trying to burn sugar on
top of beta-oxidation
okay let's take this into the real world
right real world here's a company that
specializes in obesogenic rat chow this
is what they do they make an obesogenic
rat chow that people pay money for this
stuff it's supposed to make you as fat
as possible as fast as possible I'm
talking visceral obesity liver fat
insulin resistance diabetes the whole
thing this this obesogenic rat chow is
very low in protein it's high in fat and
carbs it's really high in carbs if you
look at the ground it's vaguely eerily
similar to the standard American diet
it's pretty sad right yeah so we know
how to make we know how to make both
animals and healings as fat fat as
possible as rapidly as possible it's
sugar and fat together right the obg
undergrad Chow is a refined process
concentrated fat and sugar mixed
together it's usually cornstarch and
vegetable oil or something like that but
it's low in protein low in nutrients
it's just sugar and fat and that is how
you get anything as fat as possible as
rapidly as possible you can feed humans
donuts it's pretty much the same thing
so we know how to get the very highest
insulin levels the most overfilled out
of the sides the worst body composition
the highest fat mouth the lowest lean
mass you do that by feeding high carb
and high fat right and you keep
everything else low sugar and fat this
is a absolute worst we also know how to
get your adipocytes the very smallest
and how to get the very lowest infant
levels and we note that thanks to
natural bodybuilders and fitness models
and aesthetic athletes and they
accomplish this by either going well
they usually go high in protein very low
in carbs and sort of low issue in fat we
have studies that document how this is
done this is female fitness competitors
they achieve this low body fat reducing
carbohydrate intake while maintaining a
high level of protein resistance
training and moderate fat so it's
basically very low carb high protein
moderate fat and lifting so
we also know what calories got dumped
into the American diet to cause the
obesity epidemic over the past six years
right grains oils and sugars this is
flour sugar and oil or as I call it the
processed food trifecta right flour
sugar and oil in 2010 60% of all the
American calories were flour sugar and
oil we're literally eating obesogenic
rat chow and we're just maxing out all
our fat cells right ok I'm almost done I
just have like two slides left I just
want to point out that your adipocytes
are there for daily fat flux you're out
of cites are supposed to expand during
the day when you're eating shrink at
night when you're fasting and living off
of stores that and as long as you have
plenty of room for fat flux you know as
long as you're out of the sights are
empty enough that you have plenty of
room for this flux
everything's fine that's how it's
supposed to work there's also a seasonal
component to this fat flux piece all
energy on earth comes from the Sun and
the summertime there's more sunlight
plants make more sugar herbivores eat
more sugar and they get fatter
carnivores eat more fat from sadr
herbivores and they get fatter omnivores
like humans come along we more sugar and
more fat and we get really fatter the
classic example is a bear right this is
a classic omnivore and these are actual
bear out of the site's in the summer
they've got sugar
they've fruit and honey and berries and
they're also eating more fat because the
animals are salary in the summer so
they're any more sugar in fact they're
expanding our episodes they become
insulin resistant and then in the winter
time everything changes right no more
glucose at all there's no plant sugars
at all in the winter time so they're
just eating protein in fact there's also
less fat because animals are leaner in
the winter time so that's really the end
of my talk but I just want to end by
saying that in this country we've made
it summer time the peak of summer time
24 hours a day 365 days a year is just
sure if that together day after day
after day we've all maxed out or out of
the site's
half the planet insulin resistant and I
think it's time a lot of us made it
autumn you know we're there
a lot less plant sugars and way less
glucose so we can finally burn some sod
for a change and for some of it it's may
be time to make it the dead of winter
where we know glucose at all and you
know maybe even less fat so yeah that
concludes my talk yeah
[Applause]
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