SNPs of PPARG, LEP, and LEPR in Response to Influenza Vaccine

 

In this study, the association of the leptin gene (LEP), leptin receptor gene (LEPR), and the peroxisome proliferator activated receptor gamma gene (PPARG) using 11 single nucleotide polymorphisms to understand the humoral immune response to the influenza vaccine. The most common influenza vaccine is the trivalent inactivated influenza virus split containing two strains of flu antigens, A and B. These antigens promote the immune system to create protective antibodies to defend against activated influenza viruses. LEP is a gene that produces the protein leptin and regulates energy metabolism and immune response. Leptin is a protein hormone secreted by adipocytes. LEPR is the receptor on the immune cells and binds with leptin, which then regulates the proliferation and reactivity of T cells. PPARG coordinates with leptin, which plays a role in adipocyte differentiation and inflammatory response in protein interaction network. PPARG promotes recovery from the infection of influenza virus. The SNPs for all these genes were genotyped and their response to inactivated antigens were traced. The genes LEP and LEPR were the targeted genes for observation in their response to the antigens; however, the SNPs and immune response had no significant results. The PPARG had the most significant genotypic distribution with immune response to the antigens of the flu vaccine. The PPARG had a low responsiveness to the vaccine and LEPR only had low responsiveness in males and this could possibly due to women having higher concentrations of leptin. There were three SNPs seen in PPARG correlates with baseline levels of immunomodulator and vitamin D and these receptors interact with each other for the response to the influenza vaccine. The concentrations of leptin and the way receptors utilize this protein in response to flu antigens is the main influence of how these genes handle recovery and defense against antigens.

https://www.frontiersin.org/articles/10.3389/fgene.2021.725538/full

https://www.hormone.org/your-health-and-hormones/glands-and-hormones-a-to-z/hormones/leptin

https://www.umassmed.edu/guertinlab/research/adipocytes/

Obesity Leads to Gamete Damage

Obesity can lead to a multitude of serious health problems. One that is not often discussed is the damage that it can cause to sperm production. In one experiment Zucker rats, chosen for metabolic characteristics that are close to our own, were examined for a variety of traits revolving around reproductive function. Twelve rats were selected from the same litter, some of which were over fed resulting in obesity. After being examined it was found that obesity caused many problems in regard to reproductive function.

               Among the things affected were the physical anatomy of the genitals, difference in organ weight, onset of puberty, and sperm production. The affects obesity had on sperm production were alarming. It was found that gamete production was significantly decreased as well as having notable damage to the DNA. The DNA fragmentation may result from cells that did not undergo apoptosis correctly and proceed to spermiogenesis. This is most likely due to a deficiency in leptin, a hormone that helps to regulate reproductive function.

These findings are startling to say the least as these hormones and receptors are also part of our own genome. As the obesity crisis continues on, we must start to worry about the damage being inadvertently done to future generations. Not only do future generation have to deal with the epigenetic effects of artificial additives and unknown consequences of GMO foods, but they may very well be damaged before conception.

A Genetic Mutation That Leads to Obesity

Leptin is a hormone that is produced by fat cells and involved in regulating body weight. The function of this hormone is to interact with certain areas of the brain that are involved in controlling hunger. The hypothalamus and brain stem are responsible for sending signals to the body to let it know when to stop eating. There is a small percentage of people who have a genetic mutation in their leptin gene which leads to over-eating and eventually obesity. This genetic mutation is classified as hyperleptinemia. Hyperleptinemia is a condition where there is an increase of leptin in the bloodstream. When the leptin levels are high in the body then it can lead to the development of leptin resistance. Leptin resistance is a result of increased leptin which causes fat cells to increase as well. Due to leptin resistance, the brain cannot recognize when fat cells are dramatically increasing so the body is not signaled when to stop eating which leads to obesity. The physiological causes behind the development of leptin resistance is not fully understood by most people.

Researchers have conducted an experiment involving mice to determine whether the increase of leptin in the bloodstream leads to the development of leptin resistance. The mice used in this experiment were ob/ob and wild-type. This experiment discussed the effects of how a high- fat diet impairs the sensitivity of leptin to the neurons in the hypothalamus. There was two models that were developed from this experiment. One model proposed that leptin resistance is caused by increased plasma leptin levels which leads to overstimulation of leptin receptors and activation of negative feedback loops. The second model proposed that the dietary fats are directly responsible for the development of leptin resistance. The results from the experiment showed that as the mice were fed a high- fat diet they gained significant weight over a short period of time and their ability to limit their food intake was reduced. This confirmed that the diet- induced mice were resistant to leptin even when it was injected directly into their brain. The data from the results supported that hyperleptinemia and excess leptin signaling is required in order for leptin resistance to develop. 


I think that it is important to understand the effects of leptin deficiency and leptin resistance in humans and mice, and how obesity is a resulting factor. Additionally, this experiment provided valuable information that can help people that suffer from hyperleptinemia understand how it is developed. Lastly, the findings from this experiment can be used to potentially prevent this genetic mutation from occurring.

Leptin Gene Therapy and Obesity

         

           A new study is being done on the effects of Leptin Gene therapy in rats.  Researchers have been led to believe that with this new found therapy, people suffering from obesity could see long term results in weight loss.  Leptin is a hormone secreted by adipose cells, which plays a role in regulating energy  balance by curbing hunger.  It sends signals to the brain telling a person when to stop eating.  The amount of the hormone secreted depends upon the amount of body fat a person has.  Though it has been proven that the overweight and obese population have an increased amount of this hormone, the brain actually stops responding to the hormone, causing weight gain.
            Exercise and dieting has  proven to be efficient, but over time, success depreciates. So researchers are hoping that with this new gene therapy, patients will see prolonged positive results.  More research is needed to test the efficiency and safety of this therapy, but researchers expect a positive outcome from the studies.
           I found this article very interesting.  There are so many success stories heard of people loosing hundred of pound, just to gain it all back in a few years.  There are many medical and non-medical procedures that a person can take to overcome obesity, including leptin supplements; however, none of these have proven to prolong results if someone reverts back to old habits.  I expect this research to take quite a while to determine if this therapy is safe due to the procedure, but if it does hit the market, I could see many people pleased with the results.

Check out the full article here!

Gene Mutation Leads to Obesity

In a recent article published by Science Daily says how researchers at Georgetown University Medical Center have discovered how a gene mutation can be responsible for obesity. The team at Georgetown found that a mutation to BDNF (brain derived nuerotrophic factor) gene doesn’t allow leptin and insulin to properly reach the brain. These are two hormones that are release once the body has been satisfied by the consumption of food.

Until this study was performed, researchers were clueless as to which gene controls the secretion of leptin and insulin. Even though the gene linked to obesity has been discovered, there is no cure to repair the BDNF gene. Researchers are currently experimenting different ways to repair this gene and cure adult obesity.

One Gene Mutation = Uncontrollable Obesity

In America, it seems like a major issue that is plaguing us with worry is obesity. Some of the lucky ones with a faster metabolism, allowing digestion to occur more quickly, results in a more or less slimmer figure. But has anyone ever given thought that it might be the other way around also?

Baoji Xu, Ph.D. has. As an associate professor of pharmacology and physiology at Georgetown University Medical Center, Xu has been researching a single gene mutation that occurs within the brain-derived neurotrophic factor gene (Bdnf). With this mutation, the brain does not receive the chemical signals needed, by leptin and insulin, to turn on the mechanism that suppresses the desire to keep eating, and then tells the body that it is now full. Without these signals transmitted, individuals will just keep eating until they become obese and beyond. The can never fully feel satisfied.

Until this study, it was known that the Bdnf gene has some correlation with controlling body weight. After this study, published on the Nature’s Medicine website, now we know why. Bdnf synthesis is stimulated with leptin and insulin in the dendrites on neuroglia to get their chemical message across the synapses to adjacent neurons. With the mutation of the Bdnf gene, the chemical signals cannot be passed on through the neurons, and one’s hunger will never be suppressed.