Dr. Ted Naiman - 'Insulin Resistance'

Summary

The 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

• 🌟 Chronic diseases like cancer, cardiovascular disease, and neurodegenerative diseases are largely driven by sedentary lifestyles and malnutrition, underpinned by insulin resistance.
• 📊 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.
• 🔍 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.
• 🔄 Insulin resistance is linked to the size of adipocytes (fat cells); larger adipocytes are more resistant to insulin and contribute to metabolic issues.
• 💊 Gastric bypass surgery can shrink adipocyte size, which can reverse insulin resistance and diabetes, emphasizing the importance of adipocyte size over total weight loss.
• 🍽️ 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.
• 🔄 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.
• 🚫 Glucose and fat are oxidized reciprocally in the body; an excess of glucose inhibits fat oxidation, leading to fat accumulation and insulin resistance.
• 🌱 The modern diet, high in sugars and fats, is similar to obesogenic rat chow, promoting rapid weight gain and metabolic issues.
• 🍎 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.
• 🌡️ 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

00:00

📊 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.

05:02

🔍 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.

10:04

🌐 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.

15:06

🔄 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.

20:06

🚫 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.

25:07

🍬 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.

Keywords

💡Insulin Resistance

Insulin resistance refers to the body's diminished response to the hormone insulin, which regulates blood sugar levels. In the context of the video, it is a key factor in the development of chronic diseases such as cardiovascular disease and type 2 diabetes. The speaker emphasizes that insulin resistance is often the result of poor diet and lack of exercise, leading to a state where the body's cells do not respond effectively to insulin, resulting in high blood sugar levels and potentially serious health consequences.

💡Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)

HOMA-IR is a method used to estimate insulin resistance in an individual. It is calculated using fasting glucose and fasting insulin levels and is a common measure referenced in medical literature. The video speaker mentions that an average HOMA-IR score in the country is 1.75, which is considered high, and that a score of 1.0 or lower is preferable. This concept is central to understanding how doctors can non-invasively assess a patient's insulin resistance.

💡Adipose Tissue

Adipose tissue, commonly known as body fat, is composed of cells called adipocytes. The video discusses how the size and function of adipocytes are directly related to insulin resistance. When adipocytes become too large, or hypertrophied, they can become inflamed and insulin resistant. The speaker also introduces the concept of adipocyte hyperplasia, where new fat cells are formed, which can help maintain insulin sensitivity.

💡Ectopic Fat

Ectopic fat refers to fat that is stored in locations other than the usual subcutaneous or visceral fat depots, such as in the liver, muscles, or pancreas. The video explains that when the body's fat storage capacity is exceeded, fat begins to accumulate in ectopic sites, contributing to insulin resistance and a range of health problems. This concept is crucial for understanding the systemic effects of obesity.

💡Metabolic Syndrome

Metabolic syndrome is a cluster of conditions that increase the risk of heart disease, stroke, and type 2 diabetes. The video script mentions that any marker of metabolic syndrome, such as high blood pressure, high blood sugar, excess body fat around the waist, and abnormal cholesterol levels, is linearly associated with the size of adipocytes, indicating a strong link between fat cell size and metabolic health.

💡Personal Fat Threshold (PFT)

PFT, as discussed in the video, is a concept that refers to an individual's genetic limit to how much fat they can accumulate before they become insulin resistant. It helps explain why some people may appear thin but still suffer from insulin resistance due to high levels of visceral fat. The speaker uses PFT to illustrate the genetic component of obesity and insulin resistance.

💡Lipodystrophy

Lipodystrophy is a group of rare disorders characterized by the absence or abnormal distribution of body fat. The video speaker uses lipodystrophy as an example to explain how the lack of subcutaneous fat can lead to an accumulation of visceral fat and severe insulin resistance, highlighting the importance of adipose tissue distribution in metabolic health.

💡Mitochondrial Dysfunction

Mitochondrial dysfunction refers to the impaired function of mitochondria, the organelles in cells responsible for energy production. The video script explains that individuals with obesity and insulin resistance often have defects in mitochondrial metabolism of fat, leading to reduced fat oxidation and accumulation of fat in the body. This concept is central to understanding the biochemical mechanisms behind insulin resistance.

💡Metabolic Flexibility

Metabolic flexibility is the ability of an individual to switch between different energy sources, such as glucose and fat, depending on their availability. The video emphasizes that people with good metabolic flexibility are healthier and have lower insulin levels. In contrast, those with poor flexibility struggle to adapt to changes in their diet and are more prone to insulin resistance and obesity.

💡Respiratory Quotient (RQ)

The respiratory quotient is a measure of the ratio of carbon dioxide produced to oxygen consumed during metabolism. In the video, the speaker explains that a higher RQ indicates a preference for glucose metabolism, while a lower RQ indicates fat metabolism. The RQ is used to predict future weight gain and metabolic health, with a higher RQ at baseline being associated with increased weight gain over time.

💡Glucose Toxicity

Glucose toxicity, as mentioned in the video, occurs when the excessive presence of glucose impairs the function of cells, particularly the mitochondria. This can lead to overdrive of the electron transport chain, increased reactive oxygen species, and damage to the mitochondria, contributing to insulin resistance and metabolic dysfunction.

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]