Why is a fat man still hungry

(Richard Morris) #1

This is a paradox. I like paradoxes. They tell us where our dogmas is wrong. The french paradox was that people who eat the most saturated fat got the least heart disease. That was a sign that our dogma that Saturated fat caused Heart disease was wrong.

Let’s look at just one signal, Insulin. Some of us make a lot, some of us make a little.

Insulin promotes the transcription of DNA into mRNA to make the enzyme Acetyl-CoA carboxylase (ACC) 4x. Insulin also promotes the transcoding of mRNA in our cells into ACC up to 30x via sterol response element binding protein (SREBP)-1c.

Insulin also puts energy into the ACC enzyme by phosporylating it so it can do it’s job faster. As does glucagon which in T2DMs is inadequately inhibited by insulin.

OK so what does having more ACC that has been primed for action mean?

ACC is an enzyme that potentiates the conversion of Acetyl-CoA (from any source) into Malonyl-CoA - the rate limiting enzyme for cross-converting generic fuel into storable fuel (De novo lipogenesis). Even if you have no carbs in your pipeline, if you have more insulin you will be making more Malonyl-CoA although this study focused on glucose as a driver for insulin.

Normally ACC is stimulated by signals of energy excess, namely citrate in the cytosol (a signal of ATP sufficiency) and inhibited by PalmitoylCoA which signals an excess of fatty acids. However insulin apparently drives ACC independent of those.

OK so ⇈ Insulin ⇨ ⇈ Malonyl-CoA

What does that mean?

Well Malonyl-CoA allosterically inhibits the high speed transports (Carnitine Palmitoyl Transferase enzyme embedded into the membrane of the mitochondria) that bring fatty acids longer than 16 carbons long into your mitochondria to be used for energy.


That inhibition in a hyperinsulinaemic type 2 diabetic was found (in rats) to be over 50x of that of a non diabetic.

Those fatty acids in an obese T2DM are the primary source of stored energy. That is the fat we make when we have too much energy. It is also the primary fatty acid that we store in our body fat.

To be used they have to follow a slower, more heat and peroxide (ROS) generating pathway through the peroxisomes to be cleaved into MCFAs and SCFAs that can then diffuse passively into the mitochondria.

That is why they await processing pooled in lipid droplets in cells. Those intramyocellular lipid droplets are a marker for insulin resistance in the greatest glucose sink thus driving further hyperinsulinaemia. It is also why in frank T2DMs triglycerides and NEFAs are parked unable to be used in circulation.

Remove the high insulin and now fuel is more efficiently turned into energy, and your AMPK signals to your body that you have lots of energy, and now satiety happens earlier.

Think of it like a hand basin. If the drain is open you have to run the faucet at full for a long time to come close to overflowing the hand basin. However let’s say the drain is partially clogged by hair in the drain. Then even a small flow from the faucet could overflow that basin.

Pull out that clog and the sink empties at a rate that is mostly independent of the faucet refill rate.

The water going down the drain in this metaphor is the process of turning fuel into energy, it is our mitochondria turning glucose, fatty acids, or protein into ATP. The faucet is taking in more or less fuel as food. The overflowing basin is stored fuel - body fat. And of course the hair clog is insulin inhibiting getting fuel into your engine.

For such a person limiting non-caloric nutrients to essential requirements and eating a source of energy that does not clog the hand basin means that energy freely flows from source (storage and intake) to sink (muscle cells being the largest sink). Satiety signals are driven in part by the conversion of fuel to energy (incl: AMPK).

In other words a person eating to satiety will eat less. The faucet is coupled to the drain throughput. The more energy is being generated (water flowing through the drain) the less food intake is required (water from the faucet). As the creation of energy drops (the flow through the drain drops) satiety signals cue the intake of more fuel (turn up the faucet).

That is why “Fat to Satiety” works to reduce the insulin demand in over 90% of participants on the Virta study and reverse the diabetes of over 60% of subjects in 1 year. And as a nice side effect, it additionally reduces their stored energy (body fat) for self evident reasons. Prof Phinney and Dr Hallberg pulled the clog out of their hand basin and their faucets turned down while the basin emptied and then once the basin was empty the faucet turned back up again.

This is also why the Ebberling/Ludwig 2018 paper showed that for every step reduction of carbohydrate intake the metabolic rate rose. It Dr Ludwigs subjects some had no blockage, some had some a slight blockage in the drain, and some had dropped a hand washer in the sink stopping most of the flow and he was able to observe that depending on what was in the drain changed the rate that water flowed through the drain.

It is also why Kevin Halls Met. Ward studies using isocaloric feeding don’t show an advantage because in Kevin Halls hand basin when you turn down the faucet to a hypocaloric drip, every sink empties. Calories in Calories out, FTW!

(Karen) #2

Clearly becoming and academic. Thanks for the translation at the bottom. I need more faaaaaaat

(I Am The Egg Man ku-ku-kachoo) #3

Ya know… This might be the answer I’ve been skirting around for the last month. Getting my diet properly defined and corralled has been like nailing jello to a tree…it seems I’m constantly drifting a little this way or that way, until my proteins are low one week then high the next, or the same with calories or carbs.
The one facet I’ve allowed to slide a bit, citing the rule of “Eating to Satiety” has been FAT. Looking back, my fat intake has been dropping…perhaps too much?
This WOE seems so easy at times and yet so complex at others…

(Bob M) #4

Although Kevin Hall believes the Ebberling/Ludwig 2018 paper did not show a benefit to low carb in metabolic rate:

(So much bacon . . . so little time . . .) #5

While I don’t always understand Peter, he has a way of getting to the heart of the matter. Besides, no one who dislikes Keven Hall as much as he does can be all bad!

(57da1864057add858d6f) #6

I’m very curious about why well respected low carb figures like Ted Naiman advocate increasing protein rather than fat as a more efficacious way to utilize stored energy and increase satiety…

(Bob M) #7

Peter is over my head, too, many times. His Protons series, for instance, where he lays out his theory that PUFAs cause your fat cells to be insulin sensitive (bad) and saturated fat cause your fat cells to be insulin resistant (good), the very first post in that series is quite difficult to understand. There are others in the series that are easier to understand, though.

I bought a continuous glucose monitor, to prove that high protein meals caused higher blood sugar, to prove Ted Naiman wrong. What I found was that, for me, high protein does little if anything to my blood sugar, and makes me feel much more satiated than does eating fat. I ate meals of 160+ grams of protein in a single meal. No increase in blood sugar. Felt satiated. Meanwhile, I can eat fat until it comes out my ears and I’m not satiated.

(Teri) #8

From my understanding, it takes longer for the body to digest protein, so you feel fuller longer. And protein has less calories per gram (protein=4, fat=9), so you can eat more of it in the first place. Plus, the myth about too much protein turning to “sugar” and throwing you out of ketosis is just that - a myth.



The following is just a theoretical question…
So using this model
Why do I get hungry
I have not plugged my basin (I am low carbing, high fatting, eating twice a day, no snacking, no sweeteners)
I am obese so there is plenty of fat for the body to use
But it does not use it (or it uses it for a bit then stops and tells me to eat more)
What is the explanation for that?

(Richard Morris) #10

What is your fasted insulin.

  • Someone who can get insulin to drop when they just moderately cut out carbs, can turn fuel (stored or input) into energy.
  • Someone who can only get insulin to drop when the cut carbs drastically and limit protein can also turn fuel into energy when they do that.
  • Someone who has to fast for several days to start burning body fat probably has high fasted (as in just a 10 hour fast before a blood test) insulin.

We’re all on a continuum.

What lowers fasted insulin? I wish we knew. Mine is 23.7 mIU/l. Some tissue in my body is keeping my lowest point elevated.

There is a law called Lebig’s law of the minimum that uses an image of staves of varying lengths in a barrel that is then filled with water - the water level stops at the lowest stave.


In the case of a human, and insulin, there are multiple insulin sensitive tissues that can dial up or down how much insulin is secreted in the body. Each of these are staves that can dial up more or less insulin. Whichever stave votes for the most insulin wins - and all the other tissues become more insulin resistant in defense.

  1. The hypothalamus in the brain can control insulin via the vagus nerve, and can become insulin resistant.
  2. The alpha cells of the pancreas can become insulin resistant and can dial up insulin secreted in the beta cells by secreting more or less of the hormone glucacon.
  3. Fat cells can obvious become insulin resistant through being unable to physically take on more energy under the instructions of insulin, and they can release more or less byproducts of fat breakdown called monoacylglycerol which potentiates glucose stimulated insulin secretion.
  4. Muscle cells can become insulin resistant, and they are the greatest insulin mediated sink of glucose.
  5. And the liver can drive insulin secretion and also become insulin resistant.

And I’m sure there are others.

So the short answer is … it’s likely multifactorial. When I was 100lbs overweight it was probably fat driving my insulin. Once I’d lost 1/4 of my body weight fat was no longer the lowest stave. Prof Noakes thinks the liver play a major role. Dr Catherine Crofts thinks it could be the alpha cells in the pancreas. I suspect the hypothalamus may be a culprit.

My best advice is keep calm and keto on - focus on anything that drives glucose and/or insulin. , sleep, sun exposure, high intensity exercise, meditate. Eventually your homeostasis will hopefully ratchet down whatever tissue is driving and another will take over, and that too will ratchet down and eventually not spiking insulin will mean your fasting level will drop to a normal level.

(I Am The Egg Man ku-ku-kachoo) #11

Thanks for the visual analogy. You managed to explain this in a way even I understood. That said, this saddens me: I’m undoubtedly not alone in the camp of ketoers who were hoping for a simpler resolution to a lifetime of insulin resistance problems. Ah well, back to the process.

(Richard Morris) #12

It’s a simple treatment to make circulating glucose levels not dependent on pancreatic insulin secretion, by relying on the livers ability to make glucose. That’s the primary treatment and it reverses diabetic symptoms (that even people who have not yet been diagnosed diabetic suffer).

Time as a hyperinsulinaemic did the damage of making you increasingly more resistant. Time at the lowest level you can manage will do the opposite.

Once you lose the weight that hyperinsulinaemia was keeping in your fat tissue, and you reach a new homeostasis it’s time to “keep calm and keto on” :slight_smile:

(I Am The Egg Man ku-ku-kachoo) #13

Thanks for the reply, Richard.
This, I can do. I suppose it’s only reasonable to need a prolonged period of very low insulin levels to help rebalance what happened to my body during a decade (or more) of very high levels.

I’m thankful that I’m one of the lucky ones who can easily get by without carbs or sweets. It makes the lifestyle much easier to maintain.

(Bob M) #14

I think that’s why longer term fasting helps some people, including me.

The problem with fasting insulin for me is that it’s all over the map:


My HbA1c goes down but my fasting insulin goes up? Before my 10/31/16 test, I was doing a ton of longer term fasting, yet my insulin was high? Then I went on vacation, ate more consistently, relatively low carb but some splurges, get tested two weeks later, and my insulin goes down?

It would help if we had a blood insulin test we could do with a meter, similar to the blood sugar and ketone tests we do. I think that would be more helpful than those two tests. We could test different proteins/meats/dairy products, carbs, vegetables, etc., test multiple times per day, and the like.

Maybe insulin is like my blood sugar: gets lowest around midnight, then goes up all day until about noon, then goes down all day until midnight?

(I Am The Egg Man ku-ku-kachoo) #15

Amen. This one, important measure I’ve resigned to leaving in a gray area.