Potential Therapy for Obesity-related Inflammation Identified

Potential Therapy for Obesity-related Inflammation Identified

A research team at the National Institutes of Health (NIH) recently discovered a potential molecular target useful for reducing inflammation caused by obesity. Scientists have known for some time that over-eating regularly causes inflammation in obese people, aggravating diseases such as asthma and type 2 diabetes. But a newly published study in the Journal of Clinical Investigation, entitled “Fasting and refeeding differentially regulate NLRP3 inflammasome activation in human subjects,” found that a SIRT3 protein may provide resistance to this inflammatory reaction and could prevent or even reverse obesity-related inflammation diseases.

Lead scientist Michael N. Sack, MD, and a senior researcher at NIH’s National Heart, Lung and Blood Institute, explained how his team identified SIRT3 in a study of 19 healthy volunteers who refrained from eating for 24 hours before being fed a fixed-calorie meal.

“Previous research has shown that intermittent fasting or intermittent calorie restriction — by way of eating fewer calories for a few days a month — reduces inflammation,” said Dr. Sack. “We found through our study that this effect is mediated, in part, on a molecular level when SIRT3 blocks the activity of another molecule known as the NLRP3 inflammasome.” This is because NLRP3 inflammasomes are part of an intracellular immune reaction that happens when mitochondria are put under stress — the kind that would happen from caloric over-consumption.

Using cultured cells from a control group of eight participants who continued eating as they normally would, Dr. Sack’s team found evidence suggesting that SIRT3 could be activated not just through fasting but also through the use of a vitamin B derivative, nicotinamide riboside. “Taken together, these early results point to a potential mechanism for addressing obesity-related inflammation, and thus diseases linked to this type of inflammation, such as asthma, Type 2 diabetes, rheumatoid arthritis, and atherosclerosis — which are usually conditions related to a hardened quality of life.”

Obesity is one of the biggest health concerns of our time, affecting over a third of the adult population and around 17 percent of children, according to the U.S. Centers for Disease Control and Prevention. But because this is a complex condition, obesity-related health issues may delay the management of obesity itself. “It is a vicious cycle,” said Dr. Sack. “Take asthma for example. An increase in obesity incidence has been associated with an increase in asthma incidence, but asthma makes it difficult for some to be physically active enough to lose weight.”

Now Dr. Sack and his team are beginning a complementary study at the NIH Clinical Center to analyse if the Vitamin B derivative, nicotinamide riboside, can contribute to reduce bronchial inflammation in asthma patients. If the study is successful, the research team will start larger clinical trials to verify the findings and help to find new treatments for obesity-caused asthma inflammation.

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