Saturday, June 6, 2009

Your Elephant Stepped on my Coffee Table

Take a look at this press release:

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.