Fructose reprogrammes glutamine-dependent oxidative metabolism to support LPS-induced inflammation

salvio

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Abstract​

Fructose intake has increased substantially throughout the developed world and is associated with obesity, type 2 diabetes and non-alcoholic fatty liver disease. Currently, our understanding of the metabolic and mechanistic implications for immune cells, such as monocytes and macrophages, exposed to elevated levels of dietary fructose is limited. Here, we show that fructose reprograms cellular metabolic pathways to favour glutaminolysis and oxidative metabolism, which are required to support increased inflammatory cytokine production in both LPS-treated human monocytes and mouse macrophages. A fructose-dependent increase in mTORC1 activity drives translation of pro-inflammatory cytokines in response to LPS. LPS-stimulated monocytes treated with fructose rely heavily on oxidative metabolism and have reduced flexibility in response to both glycolytic and mitochondrial inhibition, suggesting glycolysis and oxidative metabolism are inextricably coupled in these cells. The physiological implications of fructose exposure are demonstrated in a model of LPS-induced systemic inflammation, with mice exposed to fructose having increased levels of circulating IL-1β after LPS challenge. Taken together, our work underpins a pro-inflammatory role for dietary fructose in LPS-stimulated mononuclear phagocytes which occurs at the expense of metabolic flexibility.


I suppose that fructose isn't so well as Ray Peat said.
 
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Fructose from corn is far different than fructose from fruit. Ray Peat is still right.


"Fructose intake has increased substantially throughout the Western world, largely attributed to elevated sucrose and high fructose corn syrup consumption9 and is thought to exacerbate various non-communicable conditions such as obesity, type 2 diabetes and non-alcoholic fatty liver disease9. Chronic fructose consumption in these conditions has recently been shown to drive hepatic fructolysis, where the expression of lipogenic genes is enhanced10,11,12."
 

Sitaruîm

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Female C57/B6J mice aged 8–10 weeks were randomly assigned either to 10% glucose water or 10% glucose/fructose (stock solution at 60% fructose and 40% glucose) water for 2 weeks prior to LPS challenge. Mice were injected intraperitoneally with LPS from E. coli (0111:B4; Sigma L4391) at a dose of 0.1 mg/kg. Mice were sacrificed 3 h post challenge and blood collected by cardiac puncture into EDTA-coated collection tubes. Blood was spun at 2000 × g for 15 min at 4 °C and serum was collected and stored at −80 °C.
 
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Abstract​

Fructose intake has increased substantially throughout the developed world and is associated with obesity, type 2 diabetes and non-alcoholic fatty liver disease. Currently, our understanding of the metabolic and mechanistic implications for immune cells, such as monocytes and macrophages, exposed to elevated levels of dietary fructose is limited. Here, we show that fructose reprograms cellular metabolic pathways to favour glutaminolysis and oxidative metabolism, which are required to support increased inflammatory cytokine production in both LPS-treated human monocytes and mouse macrophages. A fructose-dependent increase in mTORC1 activity drives translation of pro-inflammatory cytokines in response to LPS. LPS-stimulated monocytes treated with fructose rely heavily on oxidative metabolism and have reduced flexibility in response to both glycolytic and mitochondrial inhibition, suggesting glycolysis and oxidative metabolism are inextricably coupled in these cells. The physiological implications of fructose exposure are demonstrated in a model of LPS-induced systemic inflammation, with mice exposed to fructose having increased levels of circulating IL-1β after LPS challenge. Taken together, our work underpins a pro-inflammatory role for dietary fructose in LPS-stimulated mononuclear phagocytes which occurs at the expense of metabolic flexibility.


I suppose that fructose isn't so well as Ray Peat said.

Ray Peat has already addressed these studies.

"Much of the current concern about the dangers of fructose is focussed on the cornstarch-derived high fructose corn syrup, HFCS. Many studies assume that its composition is nearly all fructose and glucose. However, Wahjudi, et al. (2010) analyzed samples of it before and after hydrolyzing it in acid, to break down other carbohydrates present in it. They found that the carbohydrate content was several times higher than the listed values. "The underestimation of carbohydrate content in beverages may be a contributing factor in the development of obesity in children," and it's especially interesting that so much of it is present in the form of starch-like materials.

Many people are claiming that fructose consumption has increased greatly in the last 30 or 40 years, and that this is responsible for the epidemic of obesity and diabetes. According to the USDA Economic Research Service, the 2007 calorie consumption as flour and cereal products increased 3% from 1970, while added sugar calories decreased 1%. Calories from meats, eggs, and nuts decreased 4%, from dairy foods decreased 3%, and calories from added fats increased 7%. The percentage of calories from fruits and vegetables stayed the same. The average person consumed 603 calories per day more in 2007 than in 1970. If changes in the national diet are responsible for the increase of obesity, diabetes, and the diseases associated with them, then it would seem that the increased consumption of fat and starch is responsible, and that would be consistent with the known effects of starches and polyunsaturated fats." -Ray Peat
 
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salvio

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Fructose from corn is far different than fructose from fruit. Ray Peat is still right.


"Fructose intake has increased substantially throughout the Western world, largely attributed to elevated sucrose and high fructose corn syrup consumption9 and is thought to exacerbate various non-communicable conditions such as obesity, type 2 diabetes and non-alcoholic fatty liver disease9. Chronic fructose consumption in these conditions has recently been shown to drive hepatic fructolysis, where the expression of lipogenic genes is enhanced10,11,12."
Fructose is fructose. I suppose that eating 100 grams of fructose per day from fruits isn't so different as eating from drink.

I suppose that lots of fats but in general lots of calories makes it a poison.

Anyway did Ray Peat said how much fructose is safe in a day?
 
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Saying fructose is fructose is like saying all eggs are the same. He says no corn fructose is safe. I haven't heard a limit on the orange juice.
 
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salvio

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Saying fructose is fructose is like saying all eggs are the same. He says no corn fructose is safe. I haven't heard a limit on the orange juice.
Corn fructose isn't safe cause is a great amount of fructose, but even with fruit you can get the same amount even with more difficult. And liver has limited capability to store it less than 100 grams.

Please supply data about what you say, otherwise this arguing is useless.

Drinking great amount of fruit juice can cause bloating and intestinal issues, so there's a limit even with these sources.
 

Michael Mohn

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I suppose that fructose isn't so well as Ray Peat said.

Ray Peat deboonked !!! LOL

PubMed Ninjas, not understand what they read. It says fructose bad bro!! It's science! :banghead:

If there is an acute infection as indicated by high lipopolysaccharides (LPS), metabolism is reduced and inflammatory reaction is upregulated. Fructose does upregulate immune reaction/inflamation in response to infections. Good !!
 
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salvio

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Ray Peat deboonked !!! LOL

PubMed Ninjas, not understand what they read. It says fructose bad bro!! It's science! :banghead:

If there is an acute infection as indicated by high lipopolysaccharides (LPS), metabolism is reduced and inflammatory reaction is upregulated. Fructose does upregulate immune reaction/inflamation in response to infections. Good !!
No. if someone has an infection immune cells try to use fructose with aerobic oxidation and in this case cancer cells and bacteria ones can reduce oxygen inside micro environment and let them die whereas with glucose they can live using just anaerobic glycolisis. Read better, please.

Up regulation of inflammation is the worse thing immune system can do, cause it destroy all the tissue creating fibrosis.
 

JudiBlueHen

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So there is HFCS in most American coca cola. I like to drink it with a heavy meal as it seems to help digestion (and mood!). Am I up-regulating my chronic cough inflammation? (I seldom have infections, colds, or flu and my lungs are clear)
 

Michael Mohn

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No. if someone has an infection immune cells try to use fructose with aerobic oxidation and in this case cancer cells and bacteria ones can reduce oxygen inside micro environment and let them die whereas with glucose they can live using just anaerobic glycolisis. Read better, please.

Up regulation of inflammation is the worse thing immune system can do, cause it destroy all the tissue creating fibrosis.

Please write better! This is incomprehensible gibberish. They can live,...let them die...who? Where in the study do they use cancer cells or bacteria? The study triggers a response in immune cells by exposing them to LPS and measuring cytokines and mmune cell metabolism. Where do cancer and bacteria come into play?
 

Michael Mohn

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Up regulation of inflammation is the worse thing immune system can do, cause it destroy all the tissue creating fibrosis.

This is fantasy. Inflamation reduces circulation and logs plasma in tissues reducing the spread of bacteria. With blood glucose deprivation the infectious bacteria can't reproduce. Inflamation protects tissues. The problem is when inflamation becomes chronic in absence of pathogens. Then tissues degenerate.
 

Eberhardt

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I stand with @Rinse & rePeat here. That debunking is thoroughly debunked as far as I know. I am not saying Peat is always right and of course he isnt- But this is no "fructose is fructose" case. HFCS is as mentioned not only fructose and in addition to the mentioned factors it is also heavily processed and supposedly has changed molecular structure (the details was much to complex for me) and I think he also mentioned it might be estrogenic and contained burnt material from the processing. Until I see something that proves this without using HFCS it still is hogwash . Consumption of fruit does not have the same statistics however much anyones eat of them. On that note, if this was to be true I would like to hear the proposed mechanism making the fructose itself unhealthy (though I wouldnt exclude the possibility that actual pure fructose that wasnt balanced with glucose like in fruit might be problematic in a certain way, (HFCS is not free of glucose, its at least 40% glucose if I remember correctly)). Mechanism for fructose being harmful? shoot :) I am open to be proven wrong
 

Sitaruîm

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Fructose from corn is far different than fructose from fruit. Ray Peat is still right.


"Fructose intake has increased substantially throughout the Western world, largely attributed to elevated sucrose and high fructose corn syrup consumption9 and is thought to exacerbate various non-communicable conditions such as obesity, type 2 diabetes and non-alcoholic fatty liver disease9. Chronic fructose consumption in these conditions has recently been shown to drive hepatic fructolysis, where the expression of lipogenic genes is enhanced10,11,12."
Did they use fructose from corn in the study? It doesn't mention that anywhere
 
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salvio

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Please write better! This is incomprehensible gibberish. They can live,...let them die...who? Where in the study do they use cancer cells or bacteria? The study triggers a response in immune cells by exposing them to LPS and measuring cytokines and mmune cell metabolism. Where do cancer and bacteria come into play?
I put what I wrote in a translator: Google Traduttore

It translate perfectly in another language, are you less intelligent as a machine or maybe the machine translate only cause I wrote badly?

Or maybe didn't you understand what I wrote cause you don't know words like aerobic and anaerobic?
 
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salvio

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This is fantasy. Inflamation reduces circulation and logs plasma in tissues reducing the spread of bacteria. With blood glucose deprivation the infectious bacteria can't reproduce. Inflamation protects tissues. The problem is when inflamation becomes chronic in absence of pathogens. Then tissues degenerate.
Bacteria can use fructose, and small amount of glucose and causing hypoglycemia, the problem is immune system that has to fight them in hypoxic field.
 

Dr. B

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Fructose is fructose. I suppose that eating 100 grams of fructose per day from fruits isn't so different as eating from drink.

I suppose that lots of fats but in general lots of calories makes it a poison.

Anyway did Ray Peat said how much fructose is safe in a day?
Saying fructose is fructose is like saying all eggs are the same. He says no corn fructose is safe. I haven't heard a limit on the orange juice.
i read that article from Peat and i didnt get the impression he said fructose from corn is bad, it seems the case is actually that the whole ingredient called "high fructose corn syrup" actually is not just pure fructose, it's actually fructose plus those "starch like materials", which aren't even measured in the calorie count. so the issue with high fructose corn syrup isnt the fructose component it seems its the starch materials which contain much more calories and are starch, not fructose. what's listed on the label is the measured fructose count but there's double or triple that in starch material apparently. so if youre consuming the mexican cokes which use just sugar not hfcs you shouldnt have that problem.
I don't think he's said fructose from one source compared to another is bad its just that the hfcs includes other things besides fructose.
like Ray seems to imply fructose is the same whether from fruits, white sugar, or honey, but white sugar lacks the vitamins and other beneficial things.
 

Michael Mohn

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I put what I wrote in a translator: Google Traduttore

...are you less intelligent as a machine or maybe the machine translate only cause I wrote badly?
Says the guy who needs a translation program to write in another language. ?

I'm not sure if your translation program is bad, if your writing is bad or you reasoning. You post a study then you make false and unsubstantiated claims and you call everybody who points out your nonsense an idiot. Maybe you're just a stronzo.
 

Michael Mohn

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i read that article from Peat and i didnt get the impression he said fructose from corn is bad, it seems the case is actually that the whole ingredient called "high fructose corn syrup" actually is not just pure fructose, it's actually fructose plus those "starch like materials", which aren't even measured in the calorie count. so the issue with high fructose corn syrup isnt the fructose component it seems its the starch materials which contain much more calories and are starch, not fructose. what's listed on the label is the measured fructose count but there's double or triple that in starch material apparently. so if youre consuming the mexican cokes which use just sugar not hfcs you shouldnt have that problem.
I don't think he's said fructose from one source compared to another is bad its just that the hfcs includes other things besides fructose.
like Ray seems to imply fructose is the same whether from fruits, white sugar, or honey, but white sugar lacks the vitamins and other beneficial things.
High fructose corn syrup is 55% fructose and 45% glucose. All the founded and unfounded claims about starchy residual molecules or heavy metal impurities in HFCS are from the past. HFCS is OK to consume according to Peat but he and others prefer cane or beet sugar.
 

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