Calorie Overdose can Short Circuit the Normal Signals to the Brain Producing Inflammation and Change
Excessive calorie intake can be a self perpetuating habit which has devastating health effects. This habit sets off a series of events which short circuits the normal signals to the brain that regulates our quantitative intake. A new study published in the October 3rd issue of the journal Cell found that overeating causes changes in the brain.
The hypothalamus, a cone shaped gland, is the mechanism which helps the body maintain homeostasis – the tendency towards a stable, constant state of equilibrium. The hypothalamus, apart from the energy balance, regulates body temperature, hunger, thirst, fatigue, anger, sexual desire, blood pressure, water balance, and circadian cycles. According to the new study conducted on mice, the hypothalamus can respond to maintain energy balance even in the absence of weight gain.
A protein called IKKbeta/NK-kappaB is normally present in the hypothalamus in large quantities. This substance is used by macrophages and leukocytes, triggering inflammation throughout the body tissues. The finding suggests that action intended to block this pathway in the brain might fight the ever-increasing spread of chronic diseases like arthritis, diabetes, heart disease, cancer and obesity.
Dongsheng Cai of the University of Wisconsin-Madison, says that "This pathway is usually present but inactive in the brain," and that he is not sure why IKKbeta/NK-kappaB, present in the hypothalamus, comes into action at the slightest provocation. Researchers speculate it may be an important element in the body's first line of defense against pathogenic invaders at some time in the distant past.
The present societal norms mobilize this pathway by 'over nutrition', which poses an unusual environmental challenge. Once triggered, the pathway becomes rife with dysfunctions, as well as resists insulin and leptin, the two important metabolic hormones in the body.
In addition, research has also revealed that 'over nutrition' can ignite inflammatory responses in the secondary metabolic tissues, including the muscles and the liver. The inflammatory responses can then cause various metabolic defects in the tissues that are liable to trigger type II diabetes. Consequently, scientists have identified IKKß as a target for anti-inflammatory therapy that was found to be effective against obesity-associated diabetes.
Yet, it cannot be said with complete conviction whether metabolic inflammation and its mediators play a role in the central nervous system. Now, researchers have confirmed that an unceasing high-fat diet doubles the activity of this inflammatory pathway in the brains of mice. Besides, researchers have concluded that the activity of the inflammatory pathway is much higher in the brains of mice who are genetically predisposed to obesity.
Researchers have also stated that enhanced activity of the IKKß/NF-kB pathway can be detached from obesity itself because infusion of either glucose or fat alone can also lead to this inflammatory brain reaction.
Additional studies have revealed that this brain activity has the potential to lead to insulin and leptin resistance. Insulin causes the body's cells to absorb blood sugar from the bloodstream, lowering blood sugar levels. Leptin, a fat hormone, on the other hand is responsible for appetite control.
Furthermore, studies have revealed that treatments preventing the activity of IKKß/NF-kB in the brains of animals can protect them from obesity.
Despite the fact that constant inflammation is by and large considered a consequence of obesity, the latest results suggest that the inflammatory reaction might also be a cause of the discrepancy that leads to obesity and associated diseases, including diabetes. According to Cai, inflammation and obesity are fairly interrelated. Copious amounts of calories itself promote inflammation, whereas obesity provides further encouragement for inflammation by feeding back to the neurons creating a vicious cycle.
The results from these studies could effectively lead to treatments that might cut short this cycle before it goes into full gear.
Moreover, the researchers have reiterated that their work marks an initial attempt to study whether inhibiting an innate immune pathway in the hypothalamus could help to calibrate the set point of nutritional balance and therefore aid in counteracting energy imbalance and diseases induced by overeating. In addition, they recognize that the significance of this strategy has yet to be realized in clinical practice; presently, most anti-inflammatory therapies have limited direct effects on IKKß/NF-B and restricted capacity to be concentrated in the central nervous system. Nonetheless, their discoveries offer potential for treating these serious diseases.
Should this become a reality, an unparalleled strategy like this would most probably offer a safe approach, given that the critical pathway appears to be unnecessary in the hypothalamus under usual circumstances, the researchers opined.