we arrive at the speculative part of the post. I've been pondering a tough question for months. Palmitic acid has aroused universal ire for its supposed effects on lipid metabolism and insulin sensitivity**. But that leaves us with a puzzling paradox: palmitic acid is precisely the fatty acid that the liver produces when we eat carbohydrate. Our bodies contain the enzymes necessary to desaturate palmitic acid, making it monounsaturated. Why don't we use them? Why does the liver choose to secrete palmitic acid into the bloodstream unmodified? A fundamental metabolic process like this does not evolve by accident.
Here's the hypothesis. I believe that palmitic acid in the bloodstream does promote insulin resistance in rodents and probably humans as well. But there's a twist: it's probably not pathological at all; it's simply serving as a reversible signal to conserve blood glucose. Let's imagine an average person's eating habits throughout the day. Breakfast is at 8:00 am, lunch is at noon, and dinner is at 7:00 pm. The meals are about 45% carbohydrate, 40% fat and 15% protein. Let's imagine the fat consumed is animal fat, which contains some palmitic acid (25-30% of fatty acids).
The carbohydrate will be absorbed, partially turned into palmitic acid in the liver, and exported as VLDL particles. The amount of palmitic acid produced depends on the intake of starch and fructose, and will be relatively small except in the case of high carbohydrate or fructose consumption. Dietary fat will be absorbed in the intestine and sent out directly as chylomicrons (another lipoprotein particle). This is delayed relative to glucose absorption, such that the palmitic acid from both sources will enter the bloodstream at a similar time (peaks roughly 4 hours post-meal). Here is a hypothetical graph of blood glucose and blood palmitic acid at different points throughout this person's day
I'm activity to altercate a anticipation drug. I'm activity to alarm it Palmitofake, and it can be developed by Pfizer, no, Fort Dodge. I decidedly animosity FD for amazement accompanying reasons.
So what does Palmitofake do? BTW, if you didn't charge any added adumbration you can acquaint this biologic is activity to bomb as there is neither an x, y or z in its name. Trust FD to spiral up (in my mind).
Palmitofake is a fluoride commissioned alternation of palmitic acerbic which irreversibly binds to the acyl-CoA alternation armpit of JNK1 and so inhibits the alleyway by which palmitic acerbic keeps GLUT4 transporters off of the corpuscle apparent membrane, accomplished body-wide.
The argumentation to this is that the lipotoxin, palmitic acerbic (nature's additional better mistake, the better was acutely cholesterol) can no best accumulate glucose out of beef and metabolism can run, hale by fat, for anytime on glucose. Woo hoo accompany on the glucose.
This abstraction is so acutely safe and absolutely in befitting with avant-garde thoughts on blazon 2 diabetes that no assurance testing is accounted all-important and it can be awash absolute to the accessible via adjustment in the bubbler water. OK, maybe as an over the adverse pill. Let's attending at a case study:
Jim has aloof done a abundant conditioning at the gym. Like absolutely abundant and, accident of all time, he forgot his Sportzaide. Sportzaide is a glucose alcohol acclimated to advance claret glucose levels during workouts, it promotes acceptable insulin beard that no fat is anytime austere and no glycogen anytime depleted. We wouldn't appetite him to lose weight from exercise would we?
So Jim is abundantly glycogen depleted for the aboriginal time in his life. It's an odd bearings but, in the aftermost few actor years, it has been accepted to appear occasionally to the hominids who eventually became us. It's alleged not accepting annihilation to eat for a anniversary afore accepting to hunt your diner.
If Jim is in government you ability altercate that academician action is unimportant, but you would be wrong. Jim needs a anatomic brain, aloof to break alive. Whatever abroad happens, he needs some glucose for his brain. There is no animate carriage of glucose, it runs bottomward a absorption acclivity in to academician beef application GLUT1 and GLUT3. However abounding transporters are present, if claret glucose drops beneath 2.0mmol/l Jim is activity to be unwell and if it goes beneath 1.0mmol/l he's activity to be actual dead.
Jim's claret glucose drops. His alarmist would appropriately pump out lots more, but it's got none left. His pancreas has chock-full bearing insulin aloft basal ante some time ago and is now blank to mobilise glucose in any way that doesn't charge protein catabolism, and this is not absolutely a accumulation on appeal source.
In the accustomed adjustment of things Jim will, by now, be mobilising astronomic amounts of chargeless blubbery acids from his 40kg of beer gut. These chargeless blubbery acids blitz to his anatomy and accommodate an about great accumulation of energy. They don't blitz to his brain. His academician wants glucose. His academician needs glucose. His academician will accept a atmosphere anger for glucose. Ultimately it will annihilate Jim if it doesn't get it.
Jim's body, metabolically, is in starvation mode. It needs to stop crumbling glucose on his biceps and accord it to his brain. The biceps do accomplished on chargeless blubbery acids, the academician dies in a sea of activity after glucose. The ambush to blockage animate back glycogen depleted is to accumulate glucose out of any tissue that can cope after it and save about all of it for academician use.
So the aphorism is, back the anatomy is abounding with chargeless blubbery acids, all fat application tissues should stop application glucose. They should see those chargeless blubbery acids and internalise their GLUT4 transporters so they don't decay academician glucose on impaired muscle.
The bulletin to put this change in abode is palmitic acid.
Jim has a actual specific and actual austere problem. He aloof started on Palmitofake bygone as allotment of the antecedent analytic trials. As anon as he floods his anatomy with palmitic acerbic he should accept internalised his GLUT4 glucose transporters. Palmitofake stops this. He got in to the lift as an annoyed exec with a claret glucose of 2.0mmol/l, got out of the lift on a stretcher with a claret glucose of 1.0mmol/l and died afore the paramedics could get a glucose beverage up on him, with a claret glucose of 0.1mmol/l
PALMITIC ACID CAUSES INSULIN RESISTANCE. YOU WOULD BE DEAD WITHOUT IT. IT'S ADAPTIVE.
We should be attractive at what gets burst in metabolic affection at the cellular activity processing level, not cutting the messenger. And we all apperceive that low fat diets abate mitochondrial cardinal and aerial fat diets, abnormally if ketogenic, access mitochondrial numbers.
Here's the hypothesis. I believe that palmitic acid in the bloodstream does promote insulin resistance in rodents and probably humans as well. But there's a twist: it's probably not pathological at all; it's simply serving as a reversible signal to conserve blood glucose. Let's imagine an average person's eating habits throughout the day. Breakfast is at 8:00 am, lunch is at noon, and dinner is at 7:00 pm. The meals are about 45% carbohydrate, 40% fat and 15% protein. Let's imagine the fat consumed is animal fat, which contains some palmitic acid (25-30% of fatty acids).
The carbohydrate will be absorbed, partially turned into palmitic acid in the liver, and exported as VLDL particles. The amount of palmitic acid produced depends on the intake of starch and fructose, and will be relatively small except in the case of high carbohydrate or fructose consumption. Dietary fat will be absorbed in the intestine and sent out directly as chylomicrons (another lipoprotein particle). This is delayed relative to glucose absorption, such that the palmitic acid from both sources will enter the bloodstream at a similar time (peaks roughly 4 hours post-meal). Here is a hypothetical graph of blood glucose and blood palmitic acid at different points throughout this person's day
I'm activity to altercate a anticipation drug. I'm activity to alarm it Palmitofake, and it can be developed by Pfizer, no, Fort Dodge. I decidedly animosity FD for amazement accompanying reasons.
So what does Palmitofake do? BTW, if you didn't charge any added adumbration you can acquaint this biologic is activity to bomb as there is neither an x, y or z in its name. Trust FD to spiral up (in my mind).
Palmitofake is a fluoride commissioned alternation of palmitic acerbic which irreversibly binds to the acyl-CoA alternation armpit of JNK1 and so inhibits the alleyway by which palmitic acerbic keeps GLUT4 transporters off of the corpuscle apparent membrane, accomplished body-wide.
The argumentation to this is that the lipotoxin, palmitic acerbic (nature's additional better mistake, the better was acutely cholesterol) can no best accumulate glucose out of beef and metabolism can run, hale by fat, for anytime on glucose. Woo hoo accompany on the glucose.
This abstraction is so acutely safe and absolutely in befitting with avant-garde thoughts on blazon 2 diabetes that no assurance testing is accounted all-important and it can be awash absolute to the accessible via adjustment in the bubbler water. OK, maybe as an over the adverse pill. Let's attending at a case study:
Jim has aloof done a abundant conditioning at the gym. Like absolutely abundant and, accident of all time, he forgot his Sportzaide. Sportzaide is a glucose alcohol acclimated to advance claret glucose levels during workouts, it promotes acceptable insulin beard that no fat is anytime austere and no glycogen anytime depleted. We wouldn't appetite him to lose weight from exercise would we?
So Jim is abundantly glycogen depleted for the aboriginal time in his life. It's an odd bearings but, in the aftermost few actor years, it has been accepted to appear occasionally to the hominids who eventually became us. It's alleged not accepting annihilation to eat for a anniversary afore accepting to hunt your diner.
If Jim is in government you ability altercate that academician action is unimportant, but you would be wrong. Jim needs a anatomic brain, aloof to break alive. Whatever abroad happens, he needs some glucose for his brain. There is no animate carriage of glucose, it runs bottomward a absorption acclivity in to academician beef application GLUT1 and GLUT3. However abounding transporters are present, if claret glucose drops beneath 2.0mmol/l Jim is activity to be unwell and if it goes beneath 1.0mmol/l he's activity to be actual dead.
Jim's claret glucose drops. His alarmist would appropriately pump out lots more, but it's got none left. His pancreas has chock-full bearing insulin aloft basal ante some time ago and is now blank to mobilise glucose in any way that doesn't charge protein catabolism, and this is not absolutely a accumulation on appeal source.
In the accustomed adjustment of things Jim will, by now, be mobilising astronomic amounts of chargeless blubbery acids from his 40kg of beer gut. These chargeless blubbery acids blitz to his anatomy and accommodate an about great accumulation of energy. They don't blitz to his brain. His academician wants glucose. His academician needs glucose. His academician will accept a atmosphere anger for glucose. Ultimately it will annihilate Jim if it doesn't get it.
Jim's body, metabolically, is in starvation mode. It needs to stop crumbling glucose on his biceps and accord it to his brain. The biceps do accomplished on chargeless blubbery acids, the academician dies in a sea of activity after glucose. The ambush to blockage animate back glycogen depleted is to accumulate glucose out of any tissue that can cope after it and save about all of it for academician use.
So the aphorism is, back the anatomy is abounding with chargeless blubbery acids, all fat application tissues should stop application glucose. They should see those chargeless blubbery acids and internalise their GLUT4 transporters so they don't decay academician glucose on impaired muscle.
The bulletin to put this change in abode is palmitic acid.
Jim has a actual specific and actual austere problem. He aloof started on Palmitofake bygone as allotment of the antecedent analytic trials. As anon as he floods his anatomy with palmitic acerbic he should accept internalised his GLUT4 glucose transporters. Palmitofake stops this. He got in to the lift as an annoyed exec with a claret glucose of 2.0mmol/l, got out of the lift on a stretcher with a claret glucose of 1.0mmol/l and died afore the paramedics could get a glucose beverage up on him, with a claret glucose of 0.1mmol/l
PALMITIC ACID CAUSES INSULIN RESISTANCE. YOU WOULD BE DEAD WITHOUT IT. IT'S ADAPTIVE.
We should be attractive at what gets burst in metabolic affection at the cellular activity processing level, not cutting the messenger. And we all apperceive that low fat diets abate mitochondrial cardinal and aerial fat diets, abnormally if ketogenic, access mitochondrial numbers.
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