I have long since ceased reading Peter/Hyperlipid's blog for meaningful information. There are too many examples of him openly manipulating data and misrepresenting science for me to take him seriously anymore. Still, our blogs share a certain readership and his readers do participate in other internet realms where I linger or participate. As such, his blog remains on my feed reader. Peter has been on a FIRKO mouse kick lately and it has caused me to dust off a few posts from the draft bin where this mouse fits into the discussion. But his latest latest offering on FIRKO (Fat Insulin-Receptor Knock Out) just tripped my epigenetic BSA* gene switch. *BSA = Bull Sh!t Alert
In FIRKO-ise, Peter actually compares a genetically modified mouse to putting a mouse on a ketogenic diet. Really! To review, the FIRKO mouse lacks insulin receptors. As a result, this mouse is resistant to obesity on the usual obesogenic diet for rodents (high fat). This mouse's fat cells do not "see" insulin and this is the low carbers favorite gen mod rodent because it so *clearly* shows that it's all about insulin signaling in fat tissue, and Taubes is right. I'll have at the various IRKO's in an upcoming post, but the case is hardly airtight for TWICHOO.
So in this post, Peter spins a tale of how one can create a FIRKO mouse from an ordinary C57BL/6. You first "break" it by feeding it high fat crap in a bag, then switch it to a ketogenic diet. The data actually came from such a study where the mice denoted by the triangles were switched to a KD at 60 days, and as you can see, they rapidly drop weight. As Peter tells you:
Ketosis renders adipocytes insulin resistant, just like those of FIRKO mice.
This is not true, and it is misleading. The KD doesn't do anything of the sort of knocking out insulin receptors. It may down-regulate them, but there's no indication that this even occurs. There's no evidence that the adipose tissue sensitivity to insulin is altered in any way, but what's a little making shit up between friends, right? Indeed, smaller adipocytes are more insulin sensitive than larger ones, so a case could be made that the KD rapidly resolves whatever adipose-IR the obese mice are exhibiting. In any case, Peter cites this study (website seems to be down at the moment) that I discussed HERE. The KD mice lost weight to stabilize out at approximately 85% of normal body weight comparable to the calorie restricted (black dots) mice. This too, would counter what you would expect if KD actually did anything of the sort of FIRKO-ising. Peter says:
We know that simply not eating for a while induces whole body physiological insulin resistance. We also know we can do exactly the same thing, without all the pesky death involved in sustained not-eating, by simply going in to deep ketosis without cutting calories.
This is readily explained by the KD mice having a 15% higher resting metabolic rate than even the CR group ... and something that has the ketogenic crowd (all of which are eating single digit percent protein I'm sure) crowing over their metabolic advantage! But speaking of the fatty fairy tales, look at the insulin levels in the table in my post. If anything, the KD diet made these mice functionally Type 1 diabetic (insulin deficient) ... not FIRKO. Peter seems unconcerned that the KD mice lose lean and are relatively "fattier" than their CR peers. Whatever ... but the KD's avoid that pesky death? Really? Well, if they were actually FIRKO-ised, we can expect that they would live longer. As Peter rightly points out, the FIRKO mouse lives 18% longer than ad libitum fed mice on standard chow. But how about the KD mice from this study? But:
What about these ketogenic fed, pseudo-FIRKO mice? Alas the sad story of their premature demise will have to be left for the next post...
Yes, alas. Because we wouldn't want to spoil our sarcastic gloat session with the reality of what happens to these FIRKO-ised mice. The "excess fat" that may have escaped it's insulin-stimulated chains in the adipose tissue doesn't make the workings for urine derived salad dressing -- but it makes for FIRKO foie gras. These mice develop fatty livers. Surely this is a relic of the high fat crap in a bag they were fed for roughly two months. But no ... Hepatic steatosis, inflammation, and ER stress in mice maintained long term on a very low-carbohydrate ketogenic diet. I cited this study in my prior post (I have the full text now and will be blogging on this at some future date). The mice in this study were fed KD for 12 weeks and the results were not favorable. Hepatic steatosis. You can blame it on the composition of the diet, type of fat, etc.etc. It won't be explained away.
Near as I can tell, it is Peter who coined this term "physiological IR" and deemed it the "good IR". Sure, the insulin resistant state is beneficial to the organism in the glucose-deprived state. Otherwise the brain would starve. But that does not mean it is a beneficial state for any organism in the long term. Urine and beer might be beneficial hydrators if you're stranded in the desert, doesn't make them beneficial for everyday imbibing. More recently I've seen Peter question whether fatty liver is good for the person in ketosis who needs lots of fats at the ready for their liver to produce ketones. Sounds like rationalizing to me, and dangerous thinking out loud. Will we be hearing about BKNAFL (Benign Ketotic Non-Alcoholic Fatty Liver) soon courtesy of Peter? Sigh.
Do I think most humans on VLC diets have to worry? Probably not ... probably ... because most are not eating a lot more food at <10% protein and essentially ZC. Well ... except for the new leader of the Insurgency. Hope he gets this memo...