Saturday, June 6, 2009

Your Elephant Stepped on my Coffee Table

Take a look at this press release: http://www.bidmc.org/News/InResearch/2009/June/POMCNeurons.aspx

The summary is this: genetically leptin-resistant mice will become obese and develop Type II diabetes. These researchers restored leptin-sensitivity for the pro-opiomelanocortin (POMC) neurons in the arcuate nucleus (ARC), an area of the hypothalamus involved with energy regulation, including appetite and blood sugar control. As a result, the mice both lost fat AND spontaneously increased their level of activity. They did not lose fat because they were exercising, they were excercising because they were losing fat.

Now contrast that to the prevailing view of obesity and (supposedly) related health issues like diabetes: you're a lazy slob, sit on the couch, eat too much, and therefore become fat and diabetic. Gary Taubes "Good Calories, Bad Calories" laid the foundation for challenging this hypothesis, drawing on decades of research showing that energy regulation is governed by an intricate dance of hormones and the central nervous system. In this view, people overeat because they're becoming fat as a result of some malfunction in this system; correspondingly, lean people are more active for the same reason.

This latest piece of research supports the hormone hypothesis. Leptin plays a key role in energy regulation, and is manufactured by fat cells depending on how much fat they contain. More fat, more leptin. Amongst other things, leptin acts on the brain to turn off appetite, i.e., when you've stored up enough energy, stop eating. It is further hypothesized that the ARC may a play role in blood glucose control, e.g. providing CNS signals to the liver to regulate glucose manufacture. This role is certainly supported by the research linked above.

The key question becomes what causes the ARC to become leptin-resistant. The authors seem to completely miss this, instead gushing about "novel drug targets" (i.e. $$$). There are plenty of clues laying about, however. Stephan at Whole Health Source notes that leptin resistance precedes insulin resistance in the development of Type II diabetes. So what causes leptin resistance? Apart from genetic defects, this is an open question, but a reasonable conjecture would be wheat germ agglutinin (WGA), a kind of protein called a lectin which is found in grains. Lectins like WGA have the annoying capability of binding to hormone receptors. This is all the more annoying because they can avoid protease enzymes in the digestive system and pass into the blood intact (most proteins are broken into amino acids, as loading up your body with intact foreign proteins is bad juju).

WGA is so effective at binding hormone receptors that scientists regularly use it for studying these. For instance, they'll take the WGA with a radioactive substance and then see where it winds up sticking on a cell. Neurotransmitters are basically just hormones released in neuronal synapse, and scientists use it to study how things are transported in the brain. So, WGA a) binds to leptin receptors and b) wanders around your brain. And what does WGA do when it locks into your leptin receptors? Unknown, but in the test tube, at least, it blocks the effects of leptin. Hmmm, throw in insulin resistance of the liver from excess fructose, sounds like a recipe for Type II diabetes.

14 comments:

Stephan Guyenet said...

Dave,

I saw that study, it has interesting implications. I may post on it at some point as well.

I'm becoming less convinced of the WGA theory. The reason is that WGA occurs in the germ, so white flour doesn't contain much of it. I suppose it could be a factor for people eating whole wheat.

Dave said...

@Stephan,

WGA as a causal agent in metabolic syndrome certainly doesn't rise above the level of conjecture. Your point about white flour is a good one, though I'd be curious how much remains. The biggest question is whether or not the body assimilates enough WGA from dietary sources to have a significant effect. If that occurs, WGA certainly has the right properties, but that's a big "if" still dangling.

Are there other wheat lectins that remain in refined flour? I only fingered WGA because of the extensive literature on its use for studying hormone receptors etc. But another lectin might fill the bill.

danh said...

Great post as usual. I've only seen these questions on one blog (actually Stephan's) i follow but have you ever seen any comments that mention stained teeth in the first few months of following a high fat diet? If so, what could that be due to? My other question is that whenever I consume a dinner high in fat (either coconut oil, butter, olive oil, or broth) when I sleep, I can't stop scratching my scalp. By the time I wake up, I have a ton of dead skin cells under my nails. This never is the case if my dinner is low to moderate in fat. I've been eating pretty steadily low carb for the past few months now.

Thanks,
Danh Le

Dave said...

I wasn't able to find anything specific on lectin content of white flour (not that I looked to hard), but it does apparently have "agglutinating activity", which is one of the hallmarks of lectins.

Dave said...

@Danh,

No, I haven't heard of stained teeth on a low-carb diet. Maybe you're getting more of the fat soluble vitamins required for rebuilding enamel, and something else (coffee? tea?) is is getting incorporated as well? Just a wild guess.

I've never heard of the itchy scalp thing either. On a related tangent, I quit using soap and shampoo. I had both dandruff and oily hair/skin prior to this. The theory is that your body wants to make some amount of oil, soap removes this, causing it to overreact and make even more. Since quitting soap, no more dandruff, and I only get really oily skin if I have too much wheat or sugar.

Sounds gross, I know. I give my hair a vigorous scrub under hot water when I shower, and use a little baking soda paste to wash off the stinky parts. Works for me, your mileage may vary.

danh said...

Not gross at all to me, but what does your wife think? haha. I haven't eliminated soap completely (still using some organic castile shea butter soap), but I have eliminated the need to shower every day - I'll review this as the weather gets warmer though. I hear the skin is great at absorbing all the bad stuff in the water.

I also stopped brushing with toothpaste for months now as well. have you any opinions on fluoride?

Dave said...

@Danh,

Thumbs up from the wife, and she'd be the first to tell me if my personal hygiene were socially unacceptable (a good thing for a hard-core left-brainer like me :-). She actually prefers the new regimen. My skin is nicer, and I use a little baking soda paste for deodorant, works much better than anything bought in a store and doesn't smell like cologne.

danh said...

how do you make the paste? just water and baking soda?

Dave said...

@Danh,

Yes, just water and baking soda.

Stephan Guyenet said...

Dave,

Yes, there is another lectin that remains in wheat after refining-- gluten.

I don't know how much WGA remains after refining, maybe some.

Jimmy Moore said...

Included you in my Top 30 list of the best low-carb blogs today, Dave:

http://www.examiner.com/x-867-LowCarb-Lifestyle-Examiner~y2009m6d25-30-of-the-best-lowcarb-diet-and-health-blogs-on-the-Internet-today

Dave said...

Thanks Jimmy!

Jim, Guacamole Diet said...

WGA or something else, there seem to be good reasons to avoid eating grains.

Dave said...

I have yet to hear a compelling reason to eat grains at all, at least from a nutritional standpoint. It seems like there's no upside and some potential downside, which would make the choice easy.

I've been asking the question about the supposed health benefits of grains for years, and have gotten no answer. Maybe a reader can come up with something?

I did poke around for info on gluten similar to WGA, in terms of interacting with hormone receptors. Didn't find much of anything either way, which probably means it's never been tested.