mTOR is life or death

Cold Thermogenesis 4: The Holy Trinity

I just want to thank Sean Croxton for asking me to present at Paleo Summit today. The ideas discussed began with a podcast I did with Jimmy Moore, #474. Before I begin here today, I strongly suggest you listen to the Jimmy Moore podcast I did in May of 2011 as a primer for this blog post. It’s going to be a long one, so open a glass of wine as the sun sets tonight. However, I think you need to hear it all tonight since I have your attention from the Paleo Summit. I have planned for this day for some time. I am humbled to share this with you all. It was hard for me to write. If any of you remember when I first gave my initial thoughts on leptin publicly, it was on a podcast I did with Jimmy Moore in May 2011. I discussed the things that transformed my thinking back then. Most of the time I spent with Jimmy, we talked about leptin. In the beginning of the podcast, I mentioned a person who saw me injure myself as I stood up to give a lecture, and told me she knew precisely why I hurt my knee. At the time, I thought I had a good handle on these modern medicine principles she mentioned so I was a skeptical of her thoughts. She told me when I got home she was going to send me a few papers and a book to read. The book was called “The Monk Who Sold his Ferrari.” She was emphatic that I read the book before the papers. Then, she told me to read six specific papers in the order they were numbered and then reflect on what I had just read.

Central Leptin Dominance: Part 3 – King of The Hill

So now that we examined Dr. Lustig's insulin theory of metabolic control we need to take a look at the reward tracts that are located in the human brain. These tracts have been well studied and their neurochemistry is well understood. What appears not to be as well known is how the hypocretin neurons and the leptin receptor control and modulate their activity. The key point here is that the dopaminegic tracts eloquently spoken of Dr. Guyenet's reward series are the "efferent only" path that is part of the effector arm of the leptin receptor and the hypocretin neurons. This means, in English, they are playing second fiddle to the leptin receptors and are not the dominant cause of obesity. They clearly play a major role in the neuro-circutry but they do not control obesity. They carry out the action but the orders were given by someone else. One of the reasons I had a major problem with the reward series, is because of my "day job" as a neurosurgeon. I have had the opportunity to operate on many brain tumors in the reward tracts and never have I ever seen either preoperatively or postoperatively one patient develop severe morbid obesity. If these tracts were truly dominant causes this would lead neurosurgeon and neurologists to see many patients with this problem. Well, we do not. That was a big issue for me with the theory. The second issue I had with it was that when we neurosurgeon's have patients with brain tumors involving the hypothalamus we see tremendous effects on feeding, obesity and on anorexia. This is well documented and I have personally seen this in many cases. Dr. Lustig pointed this out in his AHS 2011 talk when he showed some clinical cases of craniopharyngioma's and of hypothalamic trauma's that resulted in morbid obesity.

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