Reducing Inflammation to Help Solve Obesity

Obesity is a complex problem. Research into genetics and gene-related pathways is improving our understanding of the issue and opening new doors for solution. Recent research on twins is shedding light as to exactly which gene switches are malfunctioning as a result of obesity. By “throwing the switches” into the proper position, which can be done, you can much more readily get in a position to lose weight or effectively maintain a healthy weight.

To understand what the twins research means I will place it in context. True genetic adaptation takes place over tens of thousands of years. For example, one new study shows that you are genetically predisposed to obesity if your ancestors came from Northern climates. Likewise, running is a genetic evolutionary event that is wired for fat burning. If you don’t run you’ll have a much harder time turning on your natural fat burning genes. While other genetic risk factors for obesity are sure to exist, my point is that these take tens of thousands of years to evolve.

In comparison, another problem is prenatal and postnatal programming of the nervous system. In this case numerous factors come to bear on the growing fetus, and along with events that occur during the first few weeks of life, produce “nerve imprints” that can have a life-long impact on obesity risk. I discuss these in more depth in my Prenatal Nutrition and Postpartum Nutrition sections of our website. The important point here is that imprints made on the developing nervous system are more like changes in “hardware” than “software” – like writing messages on a blank chalkboard that will determine subconscious behavior for years to come. Poor fetal programming may have an adverse affect on several generations.

The interesting thing about twins is that their genetic history is the same, and most often their prenatal and postnatal programming is also similar. It is common that twins are the same weight within a few pounds. Thus, when it is found that one twin is more overweight than the other it creates a rare opportunity to examine what the differences are that caused the problem. This means that under the influence of environmental and dietary factors various gene switches will be operating differently, even though genetics is the same. This can help everyone to understand exactly what goes wrong that causes obesity.

In a study published this week, a detailed genetic analysis of 14 different pairs of twins, wherein one twin was on average 33 lbs (20%) heavier than the other, has helped clarify the nature of the obesity problem. The researchers found that the obese twins had more abdominal fat, more fatty build up in the liver, larger fat cells, insulin resistance, and low adiponectin.

A detailed genomic analysis was performed, identifying 19 specific metabolic pathways that were inappropriately activated. 15 of these pathways involved immune-generated inflammation. The most over-activated gene (5.9 times normal) involved the recruitment of macrophages into stored fat. As I point out in another recent posting this problem is directly linked to the production of more fat cells – locking in obesity. As different from the simplistic ideas of exercising more and eating less – this data shows beyond the shadow of any doubt that resistant obesity is an inflammatory problem.

The researchers went on to prove that this set of inflammatory problems, which includes a build up of fat in all the wrong places, actually clogs metabolic function of cells. Cell engines (mitochondria) within stored were found to have less DNA in their mitochondria, indicating a seriously reduced ability to perform normally (meaning a lessened ability to burn calories). Another metabolic problem was identified for the first time: the inability to naturally use branch chain amino acids in metabolism – resulting in higher blood levels of insulin that helped to lock in insulin resistance and set the stage for diabetes risk.

These are key findings that help pinpoint precise “gene switch” problems faced by a majority of people who are overweight and can’t get their weight off simply by exercising and eating better.

In essence, the problem is one of “sprained fat,” similar to the idea of a sprained ankle. Unfortunately, the types of gene switches that are inappropriately stuck in the on position tend to self-perpetuate the problem – meaning an overweight person has great difficulty ever recovering from sprained fat and therefore has a compromised ability to burn calories as fuel. It’s like being stuck with a metabolism that just limps along and can hardly keep up.