Metabolic Changes During Fasting and Starvation

Metabolic Changes During Fasting and Starvation

November 4, 2019 23 By William Morgan


hey everyone Dr Mungli here so in
this video I will be explaining you the
metabolic changes that are going on in
our body during fasting condition and
starvation during fasting conditions
when we are going to say a person is in
fasting condition strictly speaking
fasting condition it begins 10 minutes
after the meals
that’s strictly speaking otherwise
loosely speaking so we just say two to
three hours after meals
it says a person is in fasting condition
actually that is post absorptive
condition anyway for our purpose here so
in this video I will be considering 2 to
3 hours after your last meal as a
fasting condition that’s what I have
written here so two hours after meals
and then 12 hours after meals and up to
24 hours after the meals I have this
written it as a fasting condition here
and then after that it is in days and
then in weeks now anyone who is not
taking food more than 24 hours then they
just get into starvation that is what is
referred as starvation fasting is within
24 hours we are not taking anything for
24 hours that is in fact that is
basically fasting and if you don’t take
anything more than 24 hours that is
basically referred as starvation okay
now what happens during fasting
condition or two to three hours after
the meals so two to three hours after
meals our blood glucose level falls down
so I’m going to write down the blood
glucose concentration so blood glucose
it continuously falling down and then it
will just make the constant phase okay
so this is what happens under fasting
conditions and the blood glucose this
is this line is indicative of blood
glucose all the things that I’m writing
here is in the blood so I will write it has
glucose here so glucose levels fall so
as you can see continuous fall in the
glucose level and then it just maintains
a constant phase there now as the blood
glucose level falls your insulin levels
will also fall down as the insulin level
fall so you all know glucagon levels
will rise so look I’m going to write a
glucagon level so the insulin is coming
from beta cells of pancreas and glucagon
is coming from alpha cells of pancreas
and generally insulin has got a negative
effect or inhibitory effect on alpha
cells of pancreas so as the insulin
levels fall so the glucagon level will
rise so that will be rise in the
glucagon levels and the insulin level is
falling down so it will be like this so
we have glucagon here so now what is
the metabolic effect of glucagon on our
body so you know glucagon is a catabolic
hormone as opposed to insulin insulin is
a anabolic hormone now a person is in
fasting conditions a two to three hours
after meals so slowly insulin is
dropping down and glucagon is rising
so this glucagon is going to break down
or energy sources
what are the energy sources that we have
so we have glycogen in the liver we have
glycogen in the skeletal muscle and
other tissues so glucagon it is going
to go and binds to glucagon receptors in
the hepatocytes and it’s going to break
down glycogen by stimulating an enzyme
called glycogen phosphorylase enzyme now
this degradation is going on
in the liver so Im going to write that glycogen degradation now so it starts two
to three hours after meals and it Peaks
by 12 hours and it
basically it is depleted by 24 hours of
fasting so glycogen degradation this is
the glycogen degradation here mediated
by glycogen phosphorylase and that is
stimulated by glucagon hormone so glycogen degradation starts two to three
hours of the meals peaks by twelve hours
and depletes completely by 24 hours it
can vary from person to person depending
on their carbohydrate previous carbohydrate
intake some people their glucose and
glycogen can last only for 12 hours and
some other it can last for 24 hours in a
person who is taking well-balanced diet
who is 70 kg in those people so glycogen
can lost for 24 hours
so this glycogen which is breaking down into
glucose 1-phosphate further it is
converted into glucose and that will
maintain the blood glucose level under
fasting condition so basically
person will have a fasting blood glucose
level so now what else is going on here
so as the glucagon is increased here so
as the glucagon is increased here glucagon not only breaks up glycogen
stores it is also going to break a lipid
store present in our body and where do
you have a lipid store where is the
lipid stored in our body it is stored
beneath our skin that is
adipose tissue adipose tissue has got white adipose tissue has got
triacylglycerol and this triacylglycerol can be
broken down to give energy for ourselves
so glucagon it is going to go and
activate hormone sensitive lipase
glucagon is binding to glucagon receptors on the adipose tissue and it’s
going to activate hormone sensitive
lipase and that hormone sensitive lipase
it is going to release free fatty acids
and glycerol into the blood and free
fatty acids will be taken up by
peripheral tissues almost all tissues in
our body except red blood cells and the
brain so they can use free fatty acids
for their energy so they will conduct beta oxidation process skeletal muscles
cardiocytes all other tissues
including the liver it’s going to
conduct the beat oxidation breakdown
fatty acids and releases acetyl CoA
and acetyl CoA get into TCA cycle to
give energy okay so in the influence of
glucagon so your free fatty acids floods
into the blood so I’m going to write
that now so two to three hours after
meals so free fatty acid continuously
they’re going to rise as the fasting
goes on and as the person gets into
starvation free fatty acid rises so
these free fatty acids will be used by
almost all tissues in our body except
red cells and the brain so let me
gradual means there will be
continuous rise in the
fatty acids in our body okay so now the
glycerol that is coming from triacylglycerol
as the adipose tissue is
broken down into free fatty acid and the
glycerol so glycerol is taken up by the
liver free fatty acids predominantly taken up by
the liver and the other tissues glycerol
mainly it will be taken up by the liver
so what liver does with the glycerol
glycerol it will be converted into
glucose in the liver liver has glycerol
kinase enzyme glycerol 3-phosphate
dehydrogenase enzyme and ultimately glycerol is going into glucose formation by
a process called as gluconeogenesis so
not only glycerol coming from
triacylglycerol gets into
gluconeogenesis gluconeogenesis can also
be done with using lactate
lactate is coming from red blood cells
because red blood cells they conduct
anaerobic glycolysis so in anaerobic
glycolysis you get lactate lactate gets
into the blood it will be taken up by
the liver and heart so in the liver what
happens the lactate is converted back
into glucose by gluconeogenesis now some
of the amino acids can also be converted
into glucose like out of 20 amino acids 18 of
them can be converted to glucose so
let’s see what is the timeline for
gluconeogenesis
gluconeogenesis it starts two to
three hours after meals but
it will be there at basal level so
this is the gluconeogenesis line here it
will be there at the base level because you
are still glycogen degradation is
going on so at 12 hours your glycogen
degradation is at peak and it is
depleted by 24 hours and the glycogen
degradation is depleted so the
gluconeogenesis that is going on at a
very basal level here it will start to
rise or 12 hours by 12 hours it is
steaming up and by 24 hours it is at peak gluconeogenesis is at peak by 24
hours by the time your glycogen
degradation is already down it is
totally depleted so now the glucose maintenance
this is the glucose here so the
maintenance of blood glucose level it
will be done by gluconeogenesis process
now as the gluconeogenesis process
reaches peak here by 24 hours your
gluconeogenesis is at peak by that time
you know that the glycogen degradation
degradation is already down here or total depleted
now the gluconeogenesis further it is
going to continue for at the peak level
for another one week basically for one
week it will be on peak as you can see
this is one week period here soon
gluconeogenesis is at peak and after
that it is going to fall down
gluconeogenesis is going to drop by
second week and then it just maintains
at a constant level okay so now what all
the sources there you can see as the
gluconeogenesis is falling down even
the blood glucose levels also falls
down and just maintaining a constant
pace now what all the sources for
what all the precursors for
gluconeogenesis under this condition so
initially from 2 to 3 hours and then 12
hours up to 24 hours in this particular
periods how the glucose is made it is
made from by converting glycerol into glucose glycerol you know it is coming
from triacylglycerol it is made from
converting lactate into glucose in the
liver and also some of the amino acids
present in the hepatocytes and also
amino acids coming from the muscle not
really because of breakdown of skeletal
muscles of breakdown of skeletal muscle
doesn’t go on until more than 24 hours
to 48 hours it takes 24 hours to 48
hours for our skeletal muscle proteins
to undergo proteolysis
so the amino acids that are coming from
skeletal muscle actually they are all
come they are all coming from the
transamination process what happens
during
transamination let me explain they
transamination so whenever person is in
fasting condition see there is a
glucagon is elevated releasing
free fatty acids
free fatty acids gets into the skeletal
muscles
skeletal muscles will conduct the beta oxidation
process and they will get acetyl CoA
from beta oxidation acetyl CoA level rises
as the acetyl CoA level rises acetyl CoA will have a negative
effect on pyruvate dehydrogenase complex
so that means the glucose which is
converted to pyruvate which is further
is not converted to acetyl coa because
excess acetyl CoA from beta oxidation
of fatty acids in skeletal muscle will
have a negative effect on pyruvate dehydrogenase
complex there by pyruvate accumulates
and this accumulated pyruvate it will
undergo transamination reaction so with
the glutamate amino acid glutamate so in
this transformation what happens
pyruvate is converted to alanine and
glutamate is converted to alpha keto
glutarate you can watch my video on
transamination the link for that is
appearing right now on the right upper
corner now with pyruvate undergoing
transamination it is converted to a
alanine and the alanine is coming into
the blood and that will be taken up by
the liver and that will participate in
gluconeogenesis process that is what
happens within 24 hours of this
gluconeogenesis period so the major
sources or the precursors for
gluconeogenesis within that 24 hours i
would say it is glycerol lactate and the
amino acid coming from the muscle
specially from transamination reaction
which is coming from pyruvate okay after
24 hours what happens so after 24 hours
24 to 48 hours period so it is the
proteolysis that can go on in the
skeletal muscle especially because by
that time even the cortisol will be
elevated because the person is in
starvation it’s a stressful situation so
the cortisol will build up in the blood
so that cortisol can lead to proteolysis
in the skeletal muscle and skeletal muscle proteins will be broken down to
release more amino acids so that amino
acids will go to the liver and in the
liver some of these amino acids go into gluconeogenesis process
to maintain blood glucose level and also
some amino acids in the liver can be
going into protein synthesis to make
essential proteins that are needed for
anabolic processes in the liver that is
why the skeletal muscle protein acts as a
source for amino acids in the liver
but so far that happen the
starvation has to be 24
48 hours and then continues there until
like 7 days after that you see
there is a drop in these gluconeogenesis
because by that time 50 to 60% of the
skeletal muscle is already proteolysed so
growth hormone comes in and it will
decrease the proteolysis and thereby
gluconeogenesis this drops and continues
and the constant phase and in this
gluconeogenic precursors are
glycerol and lactate again because glycerol
is coming from continuous
degradation of triacylglycerol into free
fatty acids and glycerol and the lactate
is coming from anaerobic glycolysis so
this is what happens in relation to
gluconeogenesis process now see a
the free fatty acids are coming
into the liver so liver is conducting
beta oxidation beta oxidation will give
you acetyl CoA and acetyl CoA
will saturate TCA cycle once TCA cycle
is saturated so excess acetyl CoA
they will be diverted into ketone body
formation ketone bodies for formation
note like 12 hours after fasting
they basically are at the baseline you
won’t really see them much in the blood
but after 24 hours so they start to
appear in the blood so by the three days
as you can see there is a significant
appearance of ketone bodies and they
are going to rise as the starvation like
fasting and going into starvation as the
starvation occurs ketone body rises
this is the ketones here so ketones
will rise they will appear significantly
twenty four hours after starvation and
they are continuously rise as long as
free fatty acids are available then it
now you have most of our cells when when
a person is in fasting condition
they are all like adopted like
they’re using free fatty acids as the
ketone bodies are appearing in the blood
so our cells will adopt themselves
to use ketone also specially the
brain brain takes two to three days to
adopt for ketone bodies and start using
ketone bodies as the brain start using ketone bodies by third day like around 30
percent of the energy needs of brain
will come from ketone bodies that means
it is
going to save this glucose for red blood
cells so because it knows there as the
days goes you know gluconeogenesis is
going to fall down
blood glucose level goes to go down
that means by that time your brain is
already adapting itself to use ketone bodies
by one week brain is almost using
ketone bodies as its energy source it is
sparing glucose for red blood cell
in the same way the skeletal
muscle and other tissues like heart they
all will use ketone bodies eventually
they will revert back to use of fatty
acids because ketone bodies are
predominantly used by the brain after
one to two weeks of starvation it so
this is how the metabolic adaptations
will go on in our bodies for that
there will be a lot of hormonal changes
going on so insulin dropping glucagon
increasing and later on cortisol
coming in and then growth hormone coming
in so all these hormones they will alter
the metabolic pathways and make sure
that our cells will get all the energy
that they need so in one or the other
form it initially it will be coming from
a glycogen giving glucose after that
gluconeogenesis giving glucose and then
the free fatty acids giving energy and
later body getting into keto adaptation
process so this is all about metabolic
changes that are going on during fasting
condition and starvation I hope this
video has helped you in understanding
this concept if you have any question so
kindly let me know about that in the
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