Weight gain is typically merely about CICO, barring rare genetic disorders. With an unimpaired metabolism, if you eat excess calories you will gain weight. No hormonal imbalance necessary. This is basic energy expenditure(Calories Out) to calories consumed(Calories In, thus CICO.)

Actual metabolic syndrome afflicts 30-40 percent of Americans. Not anywhere near 96 percent. Some people are just fat and diet and exercise will absolutely work metabolically to control their weight. Some people lack of willpower. Gastric bypass again proves that with caloric reduction their metabolism, in most cases, is fully capable of sustaining weight loss.

Cancer metabolism is also flexible. It does not exclusively depend on glucose and is not “starved” by removing carbs. Fats and amino acids are fair game for many cancers. Gluconeogenesis alone creates sufficient glucose to feed cancer.

4x is quite an exaggeration....

[–] jet@hackertalks.com 5 points 23 hours ago* (last edited 23 hours ago) (1 children)

Weight gain is typically merely about CICO, barring rare genetic disorders. With an unimpaired metabolism, if you eat excess calories you will gain weight. No hormonal imbalance necessary. This is basic energy expenditure(Calories Out) to calories consumed(Calories In, thus CICO.)

CICO is technically accurate, but really describes what happened after the fact, not why it happened. Plus humans are not closed systems, have many inputs and outputs not accounted for in human level CICO, nutrition labels can be off by as much as 20% for calories. Humans are NOT bom calorimeters, we don't burn our inputs to heat water (how calories are measured). Please have a look at the carbohydrate-insulin model of obesity https://lemmy.world/post/33254443 - Basically We are hormonal machines, elevated insulin drives obesity.

Actual metabolic syndrome afflicts 30-40 percent of Americans. Not anywhere near 96 percent.

I'm sorry, I misremembered the number, its actually 93% with impaired metabolic health - https://hackertalks.com/post/7340607 - https://doi.org/10.1016/j.jacc.2022.04.046 - I'm using impaired metabolic health and not metabolic syndrome, because the key problem is hyperinsulinemia not necessarily the cluster of clinical signs used for metabolic syndrome that can take years to manifest. Impaired metabolism indicates elevated insulin.

Some people are just fat and diet and exercise will absolutely work metabolically to control their weight. Some people lack of willpower.

They are fat because of the hyperinsulinemia, without the elevated insulin they wouldn't be fat (See the carbohydrate-insulin model of obesity above).

Gastric bypass again proves that with caloric reduction their metabolism, in most cases, is fully capable of sustaining weight loss.

50% bypass patients regain the weight in 2ish years https://doi.org/10.1007/s11695-007-9265-1 , because just restricting calories didn't teach those people how to eat, and how to fix their insulin. If your only eating junk food, a gastric bypass by itself can't fix your insulin (which is the core problem of obesity)

Cancer metabolism is also flexible. It does not exclusively depend on glucose and is not “starved” by removing carbs. Fats and amino acids are fair game for many cancers.

Glucose, glutamate. By the cancer as mitochondrial dysfunction model - https://hackertalks.com/post/13010967 - https://doi.org/10.1007/s10863-025-10059-w TLDR here is the energy consumption and fermentation of cancer cells and show that only glucose and glutamine can produce ATP in cancer cells. we see that cancer cells are NOT flexible and can not metabolize fat.

Gluconeogenesis alone creates sufficient glucose to feed cancer.

100% Correct, but no need to feed cancer with exogenous glucose that is not nutritionally essential. You can't STARVE cancer by removing carbs from food, but you can stop helping it accelerate.

4x is quite an exaggeration…

3.42x, but writing 4x is just easier. https://doi.org/10.1007/s00592-017-0966-1

[–] Krusty@quokk.au 4 points 22 hours ago (1 children)

Cardiometabolic function isn't the same as metabolic syndrome. Cardiometabolic function would be like a spectrum or perhaps a map. Metabolic syndrome would be the section of spectrum(say red in the rainbow) or area on the map (like a swamp) that designates the "danger zone."

Here the term "optimal" is used and that's around 7 percent as having optimal cardiometabolic function. That doesn't instantly mean 93 percent are impaired. The other classes are **intermediate, which is half of people, ** and lastly poor which was ~44 percent.

https://www.nature.com/articles/s41568-021-00388-4

https://link.springer.com/article/10.1186/s40170-020-00237-2

Fat can be oxidized for ATP via β-oxidation (look up FAO or catabolism, or see above links.) Fat → fatty acids → β-oxidation → acetyl-CoA + electron carriers → electron transport chain → ATP.

Example: Palmitic acid, a 16-carbon fatty acid, undergoes 7 rounds of β-oxidation producing 8 acetyl-CoA total. After everything runs through the Krebs cycle and electron transport chain, you end up with roughly 106 ATP. Which is a huge amount compared with glucose(1 glucose is about 30 ATP.)

[–] jet@hackertalks.com 1 points 5 hours ago* (last edited 5 hours ago)

Cardiometabolic function isn’t the same as metabolic syndrome. Cardiometabolic function would be like a spectrum or perhaps a map. Metabolic syndrome would be the section of spectrum(say red in the rainbow) or area on the map (like a swamp) that designates the “danger zone.”

Here the term “optimal” is used and that’s around 7 percent as having optimal cardiometabolic function. That doesn’t instantly mean 93 percent are impaired. The other classes are **intermediate, which is half of people, ** and lastly poor which was ~44 percent.

I'm afraid your anchored on "metabolic syndrome" when I am referring to impaired metabolism, since that is driven by hyperinsulinemia - and thus demonstrates a epidemic of elevated insulin in the population at large which is driven by persistently elevated blood glucose... which is exactly the environment cancer needs to thrive.... And not optimal does mean a degree of impairment by definition.

Thanks for those links, they do demonstrate cancer has a very interesting metabolic plasticity, but they do not definitively show fatty acid ATP synthesis, your Shilpa review even indicates FAO is down regulated in a variety of known cancer types... However, I hope when you read my references you just missed the section in the above paper, which addresses your rebuttal:

https://doi.org/10.1007/s10863-025-10059-w - Questionable Assumption 5: Fatty acid oxidation can provide sufficient ATP production through OxPhos in cancer cells

Regardless if Fatty Acids have some role to play, can we agree that glucose is very much the favored fuel? So even if we disagree on metabolic mitochondrial dysfunction as the basis of cancer, can we agree there is no benefit to feeding EXTRA glucose into a cancer patient?

After everything runs through the Krebs cycle and electron transport chain, you end up with roughly 106 ATP. Which is a huge amount compared with glucose(1 glucose is about 30 ATP.)

Yes, this is addressed in the Seyfried paper above, the problem is in dysfunctional mitochondria glucose pathways while less efficient are massively upgraded... i.e. why the PET scan works.