The Potential for Weight Loss Drugs to Reduce Inflammation
Inflammation is the body’s natural response against injury and infection, protecting against harmful events triggered by toxins, or injury. In acute situations, like cuts or infections, inflammation helps to heal and protect the body. However, chronic inflammation, which persists for several months or years, can be harmful and is linked to various health problems like heart disease, diabetes, and cancer. A recent finding has shown that glucagon-like peptide-1 receptor agonists (GLP-1RAs), can also reduce inflammation.
GLP-1 is a hormone that helps regulate blood sugar levels and has various effects on the body such as stimulating insulin release, slowing down digestion, and promoting feelings of satiety. Semaglutide-based GLP-1 drugs such as Ozempic and Wegovy, commonly used to treat type 2 diabetes (T2D) and aid in weight management, have been gaining popularity and receiving significant media attention.
A recent study has uncovered the extraordinary ability of exendin-4, which is also classified as a type of GLP-1RA. Commonly prescribed for T2D, researchers wanted to investigate if these GLP-1RAs reduce inflammation caused by immune triggers like toll-like receptor (TLR) agonists. TLRs are like sensors on the surface of immune cells and can recognize certain components that are commonly found on the surface of pathogens such as bacteria. When TLRs detect these invaders, they tell the immune system to get into action and fight off invaders by releasing inflammatory molecules such as tumor necrosis factor alpha (TNF-ɑ). TNF-ɑ is a molecule made by the body’s immune system to help fight infections. They also serve as alert flags for our bodies to signal that there is trouble. Excessive inflammation can be harmful, leading to conditions like sepsis, where the body’s response to infection becomes uncontrolled. The study investigated whether GLP-1RAs could decrease the overactive immune response.
The researchers conducted experiments using a substance known as lipopolysaccharide (LPS), a molecule found on the surface of bacteria known to trigger inflammation via TLRs. They injected mice with LPS and observed high levels of TNF-ɑ, showing that their immune system was in overdrive. However, when the mice were also given exendin-4, levels of TNF-ɑ significantly decreased.
GLP-1 is a hormone that helps regulate blood sugar levels and has various effects on the body such as stimulating insulin release, slowing down digestion, and promoting feelings of satiety. Semaglutide-based GLP-1 drugs such as Ozempic and Wegovy, commonly used to treat type 2 diabetes (T2D) and aid in weight management, have been gaining popularity and receiving significant media attention.
A recent study has uncovered the extraordinary ability of exendin-4, which is also classified as a type of GLP-1RA. Commonly prescribed for T2D, researchers wanted to investigate if these GLP-1RAs reduce inflammation caused by immune triggers like toll-like receptor (TLR) agonists. TLRs are like sensors on the surface of immune cells and can recognize certain components that are commonly found on the surface of pathogens such as bacteria. When TLRs detect these invaders, they tell the immune system to get into action and fight off invaders by releasing inflammatory molecules such as tumor necrosis factor alpha (TNF-ɑ). TNF-ɑ is a molecule made by the body’s immune system to help fight infections. They also serve as alert flags for our bodies to signal that there is trouble. Excessive inflammation can be harmful, leading to conditions like sepsis, where the body’s response to infection becomes uncontrolled. The study investigated whether GLP-1RAs could decrease the overactive immune response.
The researchers conducted experiments using a substance known as lipopolysaccharide (LPS), a molecule found on the surface of bacteria known to trigger inflammation via TLRs. They injected mice with LPS and observed high levels of TNF-ɑ, showing that their immune system was in overdrive. However, when the mice were also given exendin-4, levels of TNF-ɑ significantly decreased.
Fertilization occurs when a sperm cell meets an egg cell successfully. In the case of individuals with PCOS, this cannot occur because of ovulation, the process by which an egg is released, does not occur consistently.
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The researchers wanted to further understand how exendin-4 works to reduce inflammation and if GLP-1 RAs in the brain play a role. To investigate this, they looked at receptors in the brain and found that when GLP-1 receptors in the brain were blocked in mice, exendin-4 did not work to reduce TNF-ɑ levels. This suggested that the receptors in the brain are important for the medication to help lower inflammation.
Afterwards, they tested to see if semaglutide, a medication used to treat T2D, reduced the harmful effects of bacterial infection in mice, including sepsis. To study this, the researchers caused sepsis in mice by injecting them with a mixture of different bacteria. They then treated the mice with semaglutide and found that the mice had reduced sickness. They also did the same test with mice that didn’t have special GLP-1 receptors in their brains and found that semaglutide did not reduce sickness. To test this even further, they did experiments to block these special brain receptors and also found that the drug did not work as well. This suggests that the brain receptors are especially important for these types of drugs to work and help lower inflammation.
Overall, their findings shed light on the processes by which GLP-1 RAs reduce inflammation in the body, which could have implications for treating various diseases associated with excessive inflammation such as cardiovascular disease, metabolic disease, kidney disease, or Alzheimer's Disease.
Afterwards, they tested to see if semaglutide, a medication used to treat T2D, reduced the harmful effects of bacterial infection in mice, including sepsis. To study this, the researchers caused sepsis in mice by injecting them with a mixture of different bacteria. They then treated the mice with semaglutide and found that the mice had reduced sickness. They also did the same test with mice that didn’t have special GLP-1 receptors in their brains and found that semaglutide did not reduce sickness. To test this even further, they did experiments to block these special brain receptors and also found that the drug did not work as well. This suggests that the brain receptors are especially important for these types of drugs to work and help lower inflammation.
Overall, their findings shed light on the processes by which GLP-1 RAs reduce inflammation in the body, which could have implications for treating various diseases associated with excessive inflammation such as cardiovascular disease, metabolic disease, kidney disease, or Alzheimer's Disease.
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