By Dr. Barry Sears
The common refrain for treating obesity is simply “eat less and exercise more”. With obesity rates increasing, how is it possible that so many Americans seem to be unable to follow such simple instructions? The answer may lie in our genes.
Transcription factors are proteins that when activated, cause the expression of specific areas in our genes. This is done by activating or inhibiting cellular proteins of these transcription factors within the cell. For example, if the transcription factor NF-κB is activated, it causes the expression of inflammatory gene products. This transcription factor is activated by arachidonic acid and inhibited by omega-3 fatty acids and polyphenols. This is why reducing arachidonic acid production and increasing omega-3 fats and polyphenol intake are some of the fundamental keys to the Zone 1-2-3 Program. Reducing arachidonic acid is governed by reducing dietary intake (primarily fatty red meat and egg yolks), reducing the intake of omega-6 fatty acids or reducing insulin levels. The Zone Diet was designed to do all three.
There is another good reason to reduce insulin levels because of their inhibition of another transcription factor in the brain (actually the hypothalamus) known as the foxhead box transcription factor or Foxa2 (1). If insulin levels are low, this transcription factor is activated and causes the formation of hormones that increase spontaneous movement and alertness. If insulin levels are high, then this transcription factor in the brain is inhibited, and you become a sloth. If mice are genetically engineered to have this transcription factor constantly turned on, they are four times more active after eating a meal than normal mice or those who are obese. Furthermore, these genetically modified mice have less fat and more muscle. The same thing probably happens in humans. Not eating a lot of unfavorable carbs or calories (both protein and carbohydrates can increase insulin) at a meal will keep insulin under control. As a result you feel like exercising and have constant mental alertness instead of being lethargic and sleepy. This is the basic premise of the Zone Diet: To keep insulin in a tight zone that is not too high or too low. This new research explains why the same diet program that helps overweight and obese individuals lose weight also helps elite athletes perform better.
Of course, you could be genetically lucky and have this transcription factor constantly activated resulting in six-pack abs and ripped muscles no matter what you eat. Unfortunately, most of us aren’t that lucky, but at least we can change the expression of our genes by treating food as a drug to be taken at the right dose and at the right time to keep insulin levels in a zone.
Bottom line, the more molecular biology unravels the mystery of gene expression, the more powerful the diet becomes in controlling our DNA. That’s a pretty powerful statement.
Reference
1. Silva JP, von Meyenn F, Howell J, Thorens B, Wolfrum C, and Stoffel M. “Regulation of adaptive behaviour during fasting by hypothalamic Foxa2.” Nature 462: 646-650 (2009)