Why long

Why long-term obesity becomes irreversible
Its the brain, stupid. We should have known.
Here is the emerging view of the dysfunction of our friend, proteostasis, the cell quality control process that is at the root of more or less permanent obesity, which it saddens me to say. High-fat feeding is a major cause, which the ketosis groups claim is brain-protective. Ketones may help for some brain disorders, but one must weigh the danger of high-fat intake against that possibility.
“Combining data from our present study with those of former studies evaluating diet-induced hypothalamic inflammation, we conclude that high-fat dietary content initially induces an inflammatory process in the hypothalamus, which leads to leptin resistance, increased caloric intake, and reduced energy expenditure, resulting in the progressive increase of adiposity (4, 10, 37). Until a certain point of progression of the disease, the return to a low-fat diet will result in the complete rescue of the obese phenotype (the present data and reference 31). However, as high-fat feeding persists, hypothalamic neuronal damage will progressively contribute to the irreversibility of the disease. We propose that the anomalous activity of the ubiquitin/proteasome system in the hypothalamus is one of the mechanisms contributing to the deterioration of the system that regulates whole-body energy homeostasis. Thus, long-term obesity is accompanied by neuronal changes commonly found in classical neurodegenerative conditions, which can explain not only the refractoriness of obesity but also its frequent association with Alzheimer’s and Parkinson’s diseases (51–53).”
Ignacio-Souza, L. M., Bombassaro, B., & Pascoal, L. B. (2014). Defective regulation of the ubiquitin/proteasome system in the hypothalamus of obese male mice. Endochrinology, August, 2014.

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Jason Stoufflet

I read your post religiously, however, I disagree that obesity can reach a point where it cannot be reversed. I think folks can bad diet themselves to death, but barring the absence of other diseases or disorders, I think, a person that is simply fat…

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Bryce Lee

Yes anyone, even an obese person, can be starved into energy deficit. But, the disregulation of energy balance becomes permanent. Formerly obese people may never really be able to “trust” their hunger levels again, no matter how free of hyperpalatable …

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John Mitchell

Obesity propensity can be seen multigenerational. In addition somatosensory input from skeletal muscle fibers has hypothalamic effects upon obesity status. Lean body mass is vital for lipolysis to occur.
I’ve never had a patient who couldn’t lose weight and reverse their obesity.
Also, many times rat chow has large amounts of fat concurrent with high carb.

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John Newell

I was wondering about rat chow carb content. My n=1 ketogenic diet has resulted in the loss of 15-20 very stubborn lbs of fat.

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Duncan Ng

But mice are not humans, can’t really infer the same for humans. Also, what is the mouse chow? If high fat means omega 6 oils, probably not a good study

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Roland Fermi

Prof Arthur De Vany what is the ideal caloric composition of food intake? How much of your energy should come from fat, carbs, protein?

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John Mitchell

John, rat chow is not optimal food for them. When they get loose in the lab, the eat anything. Probably looking for nutrient-variety. They thrive on varied diets.

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Dennis C Durost

Two MDs I follow (Perlmutter and Mercola) are in ketosis 24/7/365 and both get the majority of calories from fat. Rather than being fat, both look like recent escapees from a POW camp. Not sure the mouse study is valid for humans.

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John Mitchell

Humans were never meant to be in continual ketosis.
As soon as we eat, we are immersed in the fed-state; not in ketosis.
Impossible to be 24/7/365 ketogenic…

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Arthur De Vany

I met Perlmutter and he does not look the way you describe. He looks OK. Mercola always looked skinny. But, this is about the brain. There seem to be no long-term studies of adults on ketosis; a state which is episodic, as Dr. Mitchell indicates. By the way, the study I mentioned includes human as well as mouse results. Alzheimers anyone?

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Arthur De Vany

John Mitchell Perlmutter had a whole room of products at Paleo f(x). There were products everywhere that had nothing to do with Paleo, but had some ketosis angle.

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Dennis C Durost

All the concept and idea sellers such as Perlmutter, Mercola, Kruse and even Art have a related product they wish you to partake of.

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Arthur De Vany

Even Art; but I have no products unless I eventually finish my aging book. Having a product is not a sign of deceptive claims, but it is a signal.

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John Mitchell

Arthur, thanks for your reply. I’m very much in agreement with you regarding ‘paleo died’. I take disgust at how marketing has destroyed not only healthcare, but now Paleo.

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Roland Fermi

Arthur De Vany Thanks for the answer. I get it, it’s about eating healthily and not so much about worrying over ratios.

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Prof. De Vany: what about doing
Intermittent fasting please? If obese person does
an extended fast for 2 weeks and then eats one meal a day that should probably help him to reverse obesity? Im in the fasting group where people fast for 30+ days and they lose pounds and get slim quick

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Simon Fellows

…read Jason Fungs blog or book or ADV’s book and search on here. It’s all there, or here or there.

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Simon Fellows thank you -Dr Jason Fung’s method works for obese and people
with extra weight sliming down,- thats why Im asking, but Dr Fung opposes to what professor is saying and I just would like to clarify that starvation mode isn’t feared by those who fast so they fast and lose weight and this is the only way would be to reverse and repair brain damage via autophagy

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Steve Hodges

What’s the effect of bariatric surgery on the brain?

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Arthur De Vany

Good question. No answer that I know of. If we think about it, reducing abdominal fat, a peripheral signal, must signal the brain in some way. Both leptin and insulin would decrease since both are roughly proportional to body fat. Food intake changes d…

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Frank Nova

For my part, personal observation, certain fats bring me into dépressive moods. The local tasty Lebanese chicken screw up wirth my brain.Yet, it is very “Mediterranean” in appearances. Thus, I strongly suspect cheap oils – canola in salads, sesame seed oil in the tahini sauce and chick peas puré(hummos).

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Arthur De Vany

Jack Cameron It is duration of obese years that is the issue; it is both a cause of defective brain cell trash clearing, through failure of protein qualiaty control, and the major issue leading to diabetes. It is not BMI per se, but number of years of high BMI. So, lose weight anyway and hope your stem cells repair any damage in brain cells, neurons.

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