APOΕ4 Lowers Energy Expenditure and Impairs Glucose Oxidation by Increasing Flux through Aerobic Glycolysis

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floramaria
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Re: APOΕ4 Lowers Energy Expenditure and Impairs Glucose Oxidation by Increasing Flux through Aerobic Glycolysis

Post by floramaria »

Tincup wrote:This is an excellent podcast on the topic and how ketones can modulate the effect. The meat of the podcast on this topic starts around 57:00. (StemTalk Episode 114: Lilianne Mujica-Parodi talks about how diet and ketones affect brain aging) Also this paper Diet modulates brain network stability, a biomarker for brain aging, in young adults
Thanks, Tincup! Excellent information. I found it especially interesting that in the experiment where both ketones and glucose were given the ketones still stabilized brain function. And also her statement that ketones in the brain are probably higher than those measured in the blood.
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Re: APOΕ4 Lowers Energy Expenditure and Impairs Glucose Oxidation by Increasing Flux through Aerobic Glycolysis

Post by J11 »

Hmm, the Warburg effect is highly related to cancer. Perhaps this explains the lowered cancer rate in AD. Do epsilon 33s also have lowered cancer risk? Perhaps one simple work around would be to drive OXPHOS with DCA. DCA can unblock over-reliance on PKa, though I am not sure that this applies here.

Surprised that the article did not mention the implications for cancer. APOE 4s with cancer might have therapeutic options related to this research. Cancer cells would not thrive in the low energy environment described. One also wonders how healthy it would be for APOE4s to have high lactate levels in their brains. DCA might be an option to avoid this.
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Re: APOΕ4 Lowers Energy Expenditure and Impairs Glucose Oxidation by Increasing Flux through Aerobic Glycolysis

Post by BrianR »

Tincup wrote:This is an excellent podcast on the topic and how ketones can modulate the effect. The meat of the podcast on this topic starts around 57:00. (StemTalk Episode 114: Lilianne Mujica-Parodi talks about how diet and ketones affect brain aging)
Thanks Tincup (and Fiver!). Tincup has referenced the StemTalk podcast before and I just want to add my vote for it. This podcast has had many excellent guests who discuss topics relevant to our APOE4 discussions. They tend to get far enough into the details to be useful, but not necessarily as obsessively detailed as, say, Peter Attia.

https://www.ihmc.us/stemtalks/
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Re: APOΕ4 Lowers Energy Expenditure and Impairs Glucose Oxidation by Increasing Flux through Aerobic Glycolysis

Post by J11 »

Very interesting. Hyperdrive glycolysis as immune response.

"The importance of glycolytic reprogramming in immune activation was one of the earliest observations in immunometabolism, beginning with the discovery that the immune challenge of naïve T cells produces an upregulation of glycolysis critical for T cell effector functions [26,27,28]. This increase in glycolytic flux, with the preferential conversion of pyruvate to lactate rather than oxidation in mitochondria, is akin to the Warburg effect first described in cancer and broadly characterizes the inflammatory response in both adaptive and innate immune cells [29]."

https://www.mdpi.com/2218-1989/10/11/426/htm
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Re: APOΕ4 Lowers Energy Expenditure and Impairs Glucose Oxidation by Increasing Flux through Aerobic Glycolysis

Post by nerdymel23 »

Fiver wrote: Dr. Johnson opened by explaining the theory that carriers of the apoe4 risk gene, which significantly increases the incidence of late onset Alzheimer’s disease (LOAD), process metabolic “fuels” differently. Specifically, he cited increasing evidence that apoe4 astrocytes and microglia – brain cells which tend to neurons and fight infection – are less able to process sugars by the usual processes of glycoloysis, the citric acid cycle, and/or oxidative phosphorylation (OXPHOS). He postulated that this one reason why apoe4 astrocytes fail to adequately nurture and protect neurons.

Their conclusion from this collection of experiments – some of which were recently published – was that the data support the original theory: apoe4 cells process sugars poorly and seem to use more fatty acids as fuel to compensate.

Dr. Johnson compared the metabolism of apoe4 astrocyctes and microglia to the “Warburg effect” seen in cancerous tumors. As mentioned previously many types of cancerous cells run glycolysis without the citric acid cycle and OXPHOS. This process is fast but inefficient. It churns out lactate acid as a waste product. He mentioned that a “high fat diet” made this more pronounced. NOTE: a “high-fat diet” usually refers to a poor-quality diet akin to a “Super-size Me”-type Standard American Diet, which is appropriately abbreviated as S.A.D.
Thank you Fiver and Tincup for all this wonderful information. I'm going to dig into this more. I'm intrigued by my whole Fibromyalgia/CFS experience in connection with all of this.
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Re: APOΕ4 Lowers Energy Expenditure and Impairs Glucose Oxidation by Increasing Flux through Aerobic Glycolysis

Post by Naposghost »

I just got the new iWatch and I’m tracking my oxygen while I sleep. So far so good! I’m hoping to learn more about how HBOT might help get oxygen to the brain...Possibly a useful therapy for Apoe4s.
Interesting about the iWatch. I'm an older APOE4/4 and have thought about the new iPhone to track O2 but have been worried about wearing the iWatch all night. Does it bother you?
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Re: APOΕ4 Lowers Energy Expenditure and Impairs Glucose Oxidation by Increasing Flux through Aerobic Glycolysis

Post by floramaria »

Naposghost wrote:
I just got the new iWatch and I’m tracking my oxygen while I sleep. So far so good! I’m hoping to learn more about how HBOT might help get oxygen to the brain...Possibly a useful therapy for Apoe4s.
Interesting about the iWatch. I'm an older APOE4/4 and have thought about the new iPhone to track O2 but have been worried about wearing the iWatch all night. Does it bother you?
Hi Naposghost, you quoted someone but did not capture that person’s user name in your post, so he or she won’t be notified that you have sent this question about using the iWatch all night. I tracked back through several posts hoping to find and link the person you were asking to this post. But I didn’t find the original post. If you can find the post you were quoting, you can repost your question, making sure you included the person’s user name.
You can also do a search of iWatch or any other term or phrase by by using the the magnifying glass to the left of your user name. That will let you see all previous posts containing the word or phrase. If you don’t find what you want under iWatch, you might try “ tracking O2 saturation” or some other word combo that might yield the information you are looking for. I don’t have an iWatcg]h myself so can’t offer any personal experience.
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