Guide Glycolysis and it’s positive effects on osteoblast activity | WNT3A/10B

[Mandy?]

Glycolysis and glucose metabolism in osteoblasts, by Mandy.







Hey baby,missed me? Probably not because 70% of the users here weren’t there before I was banned.
But it’s no issue,Mandy is back to teach you more!











What is the WNT3A/WNT10B pathway,how does glucose interact with it?





There’s not much to explain in such a matter,the WNT pathway is a growth pathway,that is the upstream pathway ß-catenin is produced

Regulation of osteoblastogenesis and bone mass by Wnt10b - PubMed

Wnts comprise a family of secreted signaling proteins that regulate diverse developmental processes. Activation of Wnt signaling by Wnt10b inhibits differentiation of preadipocytes and blocks adipose tissue development; however, the effect of Wnt10b on other mesenchymal lineages has not been...

pubmed.ncbi.nlm.nih.gov

Now instead of simple words like saying “WNT-10b increases bone mass and is stimulated by glucose” etc,we have to look at how it actually interacts in a osteoblastic cell.

I circled 2 areas here,one being the obvious WNT3A/WNT10b pathway,and the other being the GLUT4,1 & 3 pathways.
By the arrow (downstream effect) underneath the marked circle,there is the product of ß-catenin which I already mentioned before. ß-catenin is simple to understand if you follow the arrows,but it directly influences glycolysis

In this example here,which I like more because it shows how much glucose interacts with other pathways such as simple GLUT1 and GLUT4 interacts. Glycolysis is a direct effect that is not only influenced by the WNT10b signal,but also the IGF-1 signals that promote essential anabolism which is shown in the green circle and the insulin binding that is responsible for GLUT4. PDK1 and GLUT4 work synergistically in the TCA cycle,GLUT1 also effects AMPK indirectly by upregulating the ATP/ADP ratio.

I don’t know if you’ll be able to properly read this chart,but I’ll just tell you it’s differences in glucose availability that directly affects osteoblast activity.

Glucose is the primary fuel for osteoblasts,unlike certain tissue that switches between glycolysis and fat oxidation depending on demand,for example muscle that demands glucose upon high intensity cell activity: Osteoblasts are active all the time and are energy demanding,unlike muscle fibers that switch between types (Type I,Type IIa,Type IIx) in order to produce the certain amount of ATP that is set on demand.



this is why most ketocels like facelowIQ and rawmarcus have no dimorphism,their osteoblasts are simply sluggish.
Never go on a keto diet.





I hope you liked my guide,my bad for the formatting. Hopefully you learned something new,if you’re keto then specifically learn from this. Mandy out!

 

[Mandy?]

Tags tbh: @Currycelloser @Marlonmogsyouhaha @draftLexy ,and cause I feel nice, @Newday

 

[Marlonmogsyouhaha]

Here to save the looksmaxxing section

 

[LaWi]

Mirin effort

 

[Mandy?]

@999. New ting ting thread

 

[999.]

@999. New ting ting thread

mirin

 

[Mandy?]

No traction it’s so over

 

[Currycelloser]

Glycolysis and glucose metabolism in osteoblasts, by Mandy.







Hey baby,missed me? Probably not because 70% of the users here weren’t there before I was banned.
But it’s no issue,Mandy is back to teach you more!











What is the WNT3A/WNT10B pathway,how does glucose interact with it?





There’s not much to explain in such a matter,the WNT pathway is a growth pathway,that is the upstream pathway ß-catenin is produced
View attachment 308712
View attachment 308713

Regulation of osteoblastogenesis and bone mass by Wnt10b - PubMed

Wnts comprise a family of secreted signaling proteins that regulate diverse developmental processes. Activation of Wnt signaling by Wnt10b inhibits differentiation of preadipocytes and blocks adipose tissue development; however, the effect of Wnt10b on other mesenchymal lineages has not been...

pubmed.ncbi.nlm.nih.gov

Now instead of simple words like saying “WNT-10b increases bone mass and is stimulated by glucose” etc,we have to look at how it actually interacts in a osteoblastic cell.
View attachment 308719
I circled 2 areas here,one being the obvious WNT3A/WNT10b pathway,and the other being the GLUT4,1 & 3 pathways.
By the arrow (downstream effect) underneath the marked circle,there is the product of ß-catenin which I already mentioned before. ß-catenin is simple to understand if you follow the arrows,but it directly influences glycolysis



View attachment 308730
In this example here,which I like more because it shows how much glucose interacts with other pathways such as simple GLUT1 and GLUT4 interacts. Glycolysis is a direct effect that is not only influenced by the WNT10b signal,but also the IGF-1 signals that promote essential anabolism which is shown in the green circle and the insulin binding that is responsible for GLUT4. PDK1 and GLUT4 work synergistically in the TCA cycle,GLUT1 also effects AMPK indirectly by upregulating the ATP/ADP ratio.



View attachment 308744
I don’t know if you’ll be able to properly read this chart,but I’ll just tell you it’s differences in glucose availability that directly affects osteoblast activity.







View attachment 308753
View attachment 308755
Glucose is the primary fuel for osteoblasts,unlike certain tissue that switches between glycolysis and fat oxidation depending on demand,for example muscle that demands glucose upon high intensity cell activity: Osteoblasts are active all the time and are energy demanding,unlike muscle fibers that switch between types (Type I,Type IIa,Type IIx) in order to produce the certain amount of ATP that is set on demand.



this is why most ketocels like facelowIQ and rawmarcus have no dimorphism,their osteoblasts are simply sluggish.
Never go on a keto diet.





I hope you liked my guide,my bad for the formatting. Hopefully you learned something new,if you’re keto then specifically learn from this. Mandy out!

Glycolysis and glucose metabolism in osteoblasts, by Mandy.







Hey baby,missed me? Probably not because 70% of the users here weren’t there before I was banned.
But it’s no issue,Mandy is back to teach you more!











What is the WNT3A/WNT10B pathway,how does glucose interact with it?





There’s not much to explain in such a matter,the WNT pathway is a growth pathway,that is the upstream pathway ß-catenin is produced
View attachment 308712
View attachment 308713

Regulation of osteoblastogenesis and bone mass by Wnt10b - PubMed

Wnts comprise a family of secreted signaling proteins that regulate diverse developmental processes. Activation of Wnt signaling by Wnt10b inhibits differentiation of preadipocytes and blocks adipose tissue development; however, the effect of Wnt10b on other mesenchymal lineages has not been...

pubmed.ncbi.nlm.nih.gov

Now instead of simple words like saying “WNT-10b increases bone mass and is stimulated by glucose” etc,we have to look at how it actually interacts in a osteoblastic cell.
View attachment 308719
I circled 2 areas here,one being the obvious WNT3A/WNT10b pathway,and the other being the GLUT4,1 & 3 pathways.
By the arrow (downstream effect) underneath the marked circle,there is the product of ß-catenin which I already mentioned before. ß-catenin is simple to understand if you follow the arrows,but it directly influences glycolysis



View attachment 308730
In this example here,which I like more because it shows how much glucose interacts with other pathways such as simple GLUT1 and GLUT4 interacts. Glycolysis is a direct effect that is not only influenced by the WNT10b signal,but also the IGF-1 signals that promote essential anabolism which is shown in the green circle and the insulin binding that is responsible for GLUT4. PDK1 and GLUT4 work synergistically in the TCA cycle,GLUT1 also effects AMPK indirectly by upregulating the ATP/ADP ratio.



View attachment 308744
I don’t know if you’ll be able to properly read this chart,but I’ll just tell you it’s differences in glucose availability that directly affects osteoblast activity.







View attachment 308753
View attachment 308755
Glucose is the primary fuel for osteoblasts,unlike certain tissue that switches between glycolysis and fat oxidation depending on demand,for example muscle that demands glucose upon high intensity cell activity: Osteoblasts are active all the time and are energy demanding,unlike muscle fibers that switch between types (Type I,Type IIa,Type IIx) in order to produce the certain amount of ATP that is set on demand.



this is why most ketocels like facelowIQ and rawmarcus have no dimorphism,their osteoblasts are simply sluggish.
Never go on a keto diet.





I hope you liked my guide,my bad for the formatting. Hopefully you learned something new,if you’re keto then specifically learn from this. Mandy out!

before working out, eating 15 of glucose powder is enough to stimulate this process without disrupting u from ketosis, and u dont need more than 15 of glucose and it doesnt lead to significant increase in bonemass and strength via this pathway

 

[Mandy?]

before working out, eating 15 of glucose powder is enough to stimulate this process without disrupting u from ketosis, and u dont need more than 15 of glucose and it doesnt lead to significant increase in bonemass and strength via this pathway

Why exactly 15g?

 

[Currycelloser]

Why exactly 15g?

cause above 15 g negative effects of glucose starts also, advanced glycation end products seems to inhibit bone growth, and increasig dietary uptake of glucose doesnt lead to more bone growth stimulus via this pathway

 

[Mandy?]

cause above 15 g negative effects of glucose starts also, advanced glycation end products seems to inhibit bone growth, and increasig dietary uptake of glucose doesnt lead to more bone growth stimulus via this pathway

Advanced glycation products do not happen,even with 300g carbs daily. If you would you know already,AGEs are largely triggered by free amino acids and hyperglycemia.

 

[Mandy?]

cause above 15 g negative effects of glucose starts also, advanced glycation end products seems to inhibit bone growth, and increasig dietary uptake of glucose doesnt lead to more bone growth stimulus via this pathway

Advanced glycation products do not happen,even with 300g carbs daily. If you would you know already,AGEs are largely triggered by free amino acids and hyperglycemia.

Imagine also thinking 15g of carbs is enough to fuel even 10% of your whole body.

 

[Currycelloser]

Advanced glycation products do not happen,even with 300g carbs daily. If you would you know already,AGEs are largely triggered by free amino acids and hyperglycemia.

AGEs are triggered by free amino acids binding to glucose, and saying 300g of carbs doesnt seem to increase AGEs is false biochemically, and chronic upregulation of insulin via dietary glucose increases AGEs

 

[Mandy?]

AGEs are triggered by free amino acids binding to glucose, and saying 300g of carbs doesnt seem to increase AGEs is false biochemically, and chronic upregulation of insulin via dietary glucose increases AGEs

Chronic glucose uptake without insulin reponse=hyperglycemia
You can still consume 300g of carbohydrates without constantly causing insulin release,and it really boils down to how efficient GLUT4 vessels transport glucose.

 

[Mandy?]

AGEs are triggered by free amino acids binding to glucose, and saying 300g of carbs doesnt seem to increase AGEs is false biochemically, and chronic upregulation of insulin via dietary glucose increases AGEs

Chronic glucose uptake without insulin response=hyperglycemia
You can still consume 300g of carbohydrates without constantly causing insulin release,and it really boils down to how efficient GLUT4 vessels transport glucose.

Hyperglycemia is also merely factored of how your liver clears it’s glycogen and how well insulin reponses,which is not directly just caused by carbohydrate intake.

 

[Currycelloser]

Imagine also thinking 15g of carbs is enough to fuel even 10% of your whole body.

gluconeogenesis works for lots of functions btw

 

[Currycelloser]

Chronic glucose uptake without insulin reponse=hyperglycemia
You can still consume 300g of carbohydrates without constantly causing insulin release,and it really boils down to how efficient GLUT4 vessels transport glucose.

huh? carbs are the primary reason for spiking of insulin, even 10g of dietary carbs raise insulin no matter how healthy u are, and constant upregulation if insulin throughout the day is bad

 

[Mandy?]

gluconeogenesis works for lots of functions btw

FaceIQ ahh argument,inferior energy production and is very demanding rather than exogenous glucose.

huh? carbs are the primary reason for spiking of insulin, even 10g of dietary carbs raise insulin no matter how healthy u are, and constant upregulation if insulin throughout the day is bad

Yes,but hyperglycemia is mostly caused by poor insulin response,glucose duration in bloodstream,liver glycogen etc. insulin resistance is not even caused by the glucose molecule itself,it’s hundreds of factors,saying glucose is the main factor is like “30 guys are punching me,but only 1 carries the fault.”

 

[Mandy?]

huh? carbs are the primary reason for spiking of insulin, even 10g of dietary carbs raise insulin no matter how healthy u are, and constant upregulation if insulin throughout the day is bad

Literal linear thinking of you if you think “glucose->insulin response->insulin resistance and AGEs”

 

[Currycelloser]

FaceIQ ahh argument,inferior energy production and is very demanding rather than exogenous glucose.

proof?

Yes,but hyperglycemia is mostly caused by poor insulin response,glucose duration in bloodstream,liver glycogen etc. insulin resistance is not even caused by the glucose molecule itself,it’s hundreds of factors,saying glucose is the main factor is like “30 guys are punching me,but only 1 carries the fault.”

sure i agree with that, we dont know the causal inference of insulin resistance and there are multiple factors

Literal linear thinking of you if you think “glucose->insulin response->insulin resistance and AGEs”

huh? i never said glucose cause insulin resistance?? U said glucose uptake doesnt raise insulin always which is untrue, no matter how healthy u are, glucose cause insulin spikes and 300g of carbs, will 100% cause AGEs as it will combine with free amino acids. If u eat 300g of carbs in one meal it causes a very high insulin spike which makes u nausious but even if u split 300g of carbs multiple times a day, u will get chronic upregulation of insulin throughout the day which is still bad

 

[Mandy?]

huh? i never said glucose cause insulin resistance?? U said glucose uptake doesnt raise insulin always which is untrue, no matter how healthy u are, glucose cause insulin spikes and 300g of carbs, will 100% cause AGEs as it will combine with free amino acids. If u eat 300g of carbs in one meal it causes a very high insulin spike which makes u nausious but even if u split 300g of carbs multiple times a day, u will get chronic upregulation of insulin throughout the day which is still bad

I also never said it wouldn’t spike insulin,I meant not chronically stimulating insulin the whole day. You can reduce meal amounts from idk 4 to 2-3 meals a day,that would have at least 3-4 hour spacing. And free amino acids,could literally also be from high protein intake over of what your body usually needs to utilize. Dr.Ray Peat recommended a 7-8:1 carb to protein ratio for fully mature adults for thyroid adapating,nitrogen balance,stress. If your body is not chronically stressed,your thyroid function and other endocrine systems are in good health then your protein utilization will immediately improve. Excess protein will just cause excess sulfur,especially a lot from meat rather than dairy,due to methionine,cysteine etc,if you consume more protein than you actually need. The average mature adult just needs around 50-60g of protein. I in adolescence just consume around 70-90g,on some days around 50g. The issue is that gluconeogensis is highly demanding,your glucagon would have to be fired and in order for that to happen to need to have more adrenegic demand. Acknowledge that in a healthy person,carbs could certainly not cause issues if they eat right ones and also eat them correctly.


And by the way,let me destroy your truth more,the Randle’s cycle dosen’t exist the way you think. In order for the Randel’s cycle to be “activated”,you would need citrate accumulation,which is rather not determined by consuming carbs and fats together but rather if you have an excessive caloric intake. I’ll tell you,if the Randle’s cycle would be real,babies would literally be inflamed because they drink milk that is balanced with all 3 macronutrients.

 

[Currycelloser]

I also never said it wouldn’t spike insulin,I meant not chronically stimulating insulin the whole day. You can reduce meal amounts from idk 4 to 2-3 meals a day,that would have at least 3-4 hour spacing. And free amino acids,could literally also be from high protein intake over of what your body usually needs to utilize.

okay lets break ur arguement, this part, i agree with u, but umm high protein intake is never proven to be bad, and there is no such thing as excessive protein intake unless u eat like more than 300g of protein so yeah

Excess protein will just cause excess sulfur,especially a lot from meat rather than dairy,due to methionine,cysteine etc,if you consume more protein than you actually need. The average mature adult just needs around 50-60g of protein. I in adolescence just consume around 70-90g,on some days around 50g.

huh?? 50-60g only? thats protein deficiency bud, there is no study showing 50-60 g of protein is sufficient bruhh, ideally its 0.7 to 1.2 g per pound of body weight. also what u said, excess sulphur is a mechanistic speculation, Meat also has C15 and cycsteine does seem to reverse high methionine intake problems, not to mention glutathione and other anti oxidants, so not a problem.

The issue is that gluconeogensis is highly demanding,your glucagon would have to be fired and in order for that to happen to need to have more adrenegic demand. Acknowledge that in a healthy person,carbs could certainly not cause issues if they eat right ones and also eat them correctly.

and gluconeogenesis rates between a high carb diet and a keto diet is only 15% difference, absolute difference isnt meaningful, meaning even if u eat a high carb diet ur body will still use proteins for generating carbs via gluconeogenesis.

And by the way,let me destroy your truth more,the Randle’s cycle dosen’t exist the way you think. In order for the Randel’s cycle to be “activated”,you would need citrate accumulation,which is rather not determined by consuming carbs and fats together but rather if you have an excessive caloric intake. I’ll tell you,if the Randle’s cycle would be real,babies would literally be inflamed because they drink milk that is balanced with all 3 macronutrients.

randle's cycle is not determined by total caloric intake only but substrate availability, mainly elevated fat oxidation levels which drives citrate accumulation through metabolic intermediates. And fat oxidation leads to acetyl coenzyme A which is shown to reduce pyruvate dehydrogenase there by reducing glucose oxidation. This is shown and proven in people who eat high fat/keto diet regardless of calorie surplus or not and even tho excess citrate is exported to cytosol which inhibits 1-phosphofructokinase an important enzyme in glycolysis, the above mechanism i mentioned which is proved via studies acts independently and doesnt really depend on excess citrate nor caloric surplus.

babies have better metabolic flexibility than adults btw and also its shown that babies prefer fat oxidation rather than glycolysis too+ they have high de novo lipogenesis (DNL) activity which makes them store glucose as fat in their adipose tissue and use fat for energy, hence randle cycle does apply to infants too

 

[Mandy?]

okay lets break ur arguement, this part, i agree with u, but umm high protein intake is never proven to be bad, and there is no such thing as excessive protein intake unless u eat like more than 300g of protein so yeah

Anything that’s more than required,is excessive.

huh?? 50-60g only? thats protein deficiency bud, there is no study showing 50-60 g of protein is sufficient bruhh, ideally its 0.7 to 1.2 g per pound of body weight. also what u said, excess sulphur is a mechanistic speculation, Meat also has C15 and cycsteine does seem to reverse high methionine intake problems, not to mention glutathione and other anti oxidants, so not a problem.

There’s more than just 2 sulfur amino acids,also how can you say I’m deficient when I’m still gaining muscle at around 70g-80g~ of protein,that’s in adolescence with more body demand.

and gluconeogenesis rates between a high carb diet and a keto diet is only 15% difference, absolute difference isnt meaningful, meaning even if u eat a high carb diet ur body will still use proteins for generating carbs via gluconeogenesis.

Yeah you will generate carbs from amino acids if your carbohydrate intake is not stable.

randle's cycle is not determined by total caloric intake only but substrate availability, mainly elevated fat oxidation levels which drives citrate accumulation through metabolic intermediates. And fat oxidation leads to acetyl coenzyme A which is shown to reduce pyruvate dehydrogenase there by reducing glucose oxidation. This is shown and proven in people who eat high fat/keto diet regardless of calorie surplus or not and even tho excess citrate is exported to cytosol which inhibits 1-phosphofructokinase an important enzyme in glycolysis, the above mechanism i mentioned which is proved via studies acts independently and doesnt really depend on excess citrate nor caloric surplus.

Citrate accumulation is necessary bruvvv

babies have better metabolic flexibility than adults btw and also its shown that babies prefer fat oxidation rather than glycolysis too+ they have high de novo lipogenesis (DNL) activity which makes them store glucose as fat in their adipose tissue and use fat for energy, hence randle cycle does apply to infants too

I see no correlation

 

[Currycelloser]

Anything that’s more than required,is excessive.

and bare minimum is 0.7g of protein per pound of bodyweight

There’s more than just 2 sulfur amino acids,also how can you say I’m deficient when I’m still gaining muscle at around 70g-80g~ of protein,that’s in adolescence with more body demand.

individual experience doesnt apply to all, multiple studies and meta analysis prove that u need atleast 0.7 g of protein per lb of bodyweight for maximum MPS

Yeah you will generate carbs from amino acids if your carbohydrate intake is not stable.

irrelevant, the difference between carb rich diet and keto diet gluconeogenesis rates are only 15% which is not that significant

Citrate accumulation is necessary bruvvv

how so? thats just one pathway and as i said elevated fat oxidation levels which drives citrate accumulation through metabolic intermediates.

I see no correlation

babies dont really utilise both glucose and fats for energy, they oxidise fat for energy primarily and store carbs as fat as per randle cycle which says oxidising one substrate inhibits the other

 

[Mandy?]

and bare minimum if 0.7g of protein per pound of bodyweight

individual experience doesnt apply to all, multiple studies and meta analysis prove that u need atleast 0.7 g of protein per lb of bodyweight for maximum MPS

I still know many others that consume similar amounts of protein

irrelevant, the difference between carb rich diet and keto diet gluconeogenesis rates are only 15% which is not that significant

Merely cause ketone tone is higher.

how so? thats just one pathway and as i said elevated fat oxidation levels which drives citrate accumulation through metabolic intermediates.

You literally have to look at 2 arrows to understand.

 

[Currycelloser]

I still know many others that consume similar amounts of protein

Merely cause ketone tone is higher.

View attachment 309421
You literally have to look at 2 arrows to understand.

bro oh my god, listen, look, acetyl co A enzyme is leading to citrate accumulation okay? and fat oxidation leads to Acetyl-CoA and NADPH production, so fat oxidation indirectly contributes to citrate increase regardless of caloric surplus or intake of citrus fruits or not

 

[Mandy?]

bro oh my god, listen, look, acetyl co A enzyme is leading to citrate accumulation okay? and fat oxidation leads to Acetyl-CoA and NADPH production, so fat oxidation indirectly contributes to citrate increase regardless of caloric surplus or intake of citrus fruits or not

That’s why you generally only need like 50-70g of fat a day.

 

[Currycelloser]

That’s why you generally only need like 50-70g of fat a day.

if u are on ketosis u could go higher, and tbh, i am not in support of long term ketosis, our body is made to shift from glucose to ketosis periodically, so ideally u should be on cycles of ketosis and glycolysis tbh, so i dont recommend completely eliminating carbs from ur diet

 

[Mandy?]

if u are on ketosis u could go higher, and tbh, i am not in support of long term ketosis, our body is made to shift from glucose to ketosis periodically, so ideally u should be on cycles of ketosis and glycolysis tbh, so i dont recommend completely eliminating carbs from ur diet

Just because we historically usually had such cycles,dosen’t necessary mean you can’t eat carbohydrates all year,in my opinion.

 

[Currycelloser]

Just because we historically usually had such cycles,dosen’t necessary mean you can’t eat carbohydrates all year,in my opinion.

well, carbs and fat together could upregulate ur randle cycle, and carbs is beneficial in puberty but past that, u dont really need much carbs, and we know insulin is an aging/growth hormone, thats why igf 1 is very good for puberty but causes aging after puberty, we need to maximise longevity genes after 25 i believe and also ketones are much efficient source of energy and superior for our metabolism, carbs could combine with free amino acids causing endogenous advanced glycation end products which we dont really need. These are the reasons i dont recommend a high carb diet

 

[Mandy?]

well, carbs and fat together could upregulate ur randle cycle,

Not in circumstances of 50g,where it’s enough for regular systemic function.

and carbs is beneficial in puberty but past that, u dont really need much carbs, and we know insulin is an aging/growth hormone, thats why igf 1 is very good for puberty but causes aging after puberty, we need to maximise longevity genes after 25 i believe and also ketones are much efficient source of energy and superior for our metabolism, carbs could combine with free amino acids causing endogenous advanced glycation end products which we dont really need. These are the reasons i dont recommend a high carb diet

I literally told you,you need consistent chronic hyperglycemia to get a solid amount of AGEs,carbs do not affect aging at all,you would understand that if you weren’t affected by FacelowIQ knowledge. You would need a multitude of factors,yet you act like glucose is the only reason.