Punnett's Square

Obesity is a clear and debilitating epidemic in our society today, not only nationally, but globally as well. Researchers throughout the world have been unrelentingly searching for the easiest, fastest, and safest way to combat this problem in humans. Recently, researchers at the University of Colorado School of Medicine believe they have found the “obesity gene”, Perilipin (Plin2), that when deleted, it prevents mice from becoming obese regardless of their dietary macronutrient intake.

“When fed a diet that induces obesity these mice don’t get fat. It may be possible to duplicate this in humans using existing technology that targets this specific gene,” Prof McManaman said.

This discovery is exceedingly significant in human obesity since we possess the same exact gene, Plin2, just as mice do. If this process can be replicated in humans, that is deleting the gene Plin2, then there shows great promise to fight the mostly eternal problem of obesity that plagues the globe today. The results of the research were published in the Journal of Lipid Research.

According to a recent study conducted by researchers at the University of California Los Angeles, in addition to environmental factors such as diet and exercise, obesity is indeed linked to an individual’s genes. For 16 weeks, over 100 genetic strains of mice were treated in laboratories under identical conditions. Each were first given a healthy, well-balanced diet for a duration of 8 weeks followed by a high-sugar, high-fat content diet for the remaining 8 weeks. The results were very interesting; Although handled under the same environmental conditions, there was a prominent variation in weight gain among all of the mice. Some showed little to no change while others increased their body fat by over “600 percent.” Therefore, scientists contributed this variation to genetic influences.

If people consume a high-fat diet, the response will be predominantly determined by genetics,” Dr. Lusis said. “But whether you choose to eat a high-fat diet in the first place is largely environmental.”

Eleven genetic loci associated with obesity and fat storage were identified, several of which were ”linked to obesity in humans.” It was found that some mice had higher fat burning mechanisms, thus eliminating more calories, while others had greater propensities to be more physically active. Data from this study can greatly contribute to targeting more efficient weight loss treatments and pharmacology in the near future. In addition, researchers hope to also study more specifically “brown fat” which is metabolically responsible for creating heat and burning caloric intake. While it is certain that what one consumes and how one utilizes those calories (through exercise or inactivity) has a significant effect on fat loss and storage, it is also now inferred that obesity can be highly inheritable and pre-existent in one’s genome.

[For more on this article, check out the following links: http://www.huffingtonpost.com/2013/01/10/fat-genes-obesity-ucla-study-diet-exercise_n_2450108.html & http://healthland.time.com/2013/01/09/what-mice-can-tell-us-about-obesity-and-genetics/ ]

http://www.cnn.com/2013/02/10/health/mice-weight-loss-drug/index.html?hpt=he_c2

A University of Michigan study found an obscure drug that is used for canker sores, helped mice lose weight without having to limit calories or exercise.  A chocolate lovers dream come true. 

Dr. George Bray, a leading scientist in obesity and metabolism feels this is a tremendous development in anti-obesity drugs and relates it to the medication Viagra.  Viagra was originally developed to treat chest pain and later was found to help in the condition of erectile dysfunction.

   Researchers are getting ready to do clinical studies on the effectiveness that amlexanox would have on humans.  The drug used in an ointment treats canker sores, however, injected into mice it changed the action in genes that controls metabolism, and was not an appetite suppressant.

Should a safe and effective drug be found, it would be a phenomenal breakthrough in human weight loss and many diseases associated with obesity.

Scientists at  Virginia Commonwealth University have reversed the condition of obesity in mice by manipulating an enzyme named tyrosine-protein kinase-2 (Tyk2). The researchers had discovered that Tyk2 regulates obesity in a type of fat tissue called brown adipose tissue.(BAT) It was discovered that Tyk2 was regulated in mice by diet. When obese human fat tissue was analyzed it became apparant that the levels of tyk2 were 50% lower or more drastic. There are two different types of fat; white adipose tissue(WAT) which is responsible for energy storage, while BAT is responsible for the regulation of energy usage.  BAT activity is associated with metabolic syndrome which could impact 25% of people. This news has came at a time where 68% of Americans are overweight or obese. Those with obesity are at higher risk for cardiovascular disease, cancer, and diabetes. By activating a protein signal transducer that activated an enzyme called STAT 3 scientists were able to elevate levels of Tyk2, which in return reversed obesity in mice.

As an individual that has seen the effects of obesity in the family the news of obesity reversal is great news. The ability to for an individual to become of healthy weight not only impacts life expectancy, but also the quality of life. It amazes me what science is able to do in terms of improving the quality of life, but also hits a soft spot inside when I am able to imagine my father to have an improved quality of life. Multiple attempts have been made to help the problem, but in the end obesity has the upper hand in the battle. Just the quality of life improvement makes this discovery one that has me smiling. The health impacts as well with the reduction of cancer, diabetes, and cardiovascular disease risk could help 68% of America.

In Medical News Today, a new study was performed by Carl Ernst, a professor in the department of psychiatry at McGill University in Montreal.  This study suggests that deletion of the gene BDNF leads to major depression, anxiety, and obesity. BDNF is a nervous system growth factor that is important for brain development.  In the study, 35,000 people were referred for genetic screening, and 30,000 people were used as control.  From the genetic screening, five people tested positive for BDNF deletions.  All of them were obese and had mild to moderate intellectual impairment, plus a mood disorder.    The study conclusively links a single region of the genome to mood and anxiety.  The researchers believe their findings are a step forward in revealing new insights into the genetic underpinnings of human behavior and mood.  Ernst and his colleagues now want to test the idea that boosting BDNF may improve their brain health.

In a new study in Nature Medicine shows that the deletion of the clock gene in fat cells caused mice to become obese.  The clock gene is known as Arntl or Bmal1.  The recent findings shed light on the causes of obesity in humans.  The study was conducted by Georgios Paschos PhD, a research associate in the lab of Garret FitzGerald, MD, FRS director of the Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania.  The studies show that food consumption during what is considered the rest period for mice favored energy storage.  This caused the mice to become obese without consuming more calories.  This behavioral change in mice is similar to night-eating syndrome in humans, which is also associated with obesity.

Mice with a broken clock in their fat get fat as they eat when they should be sleeping. (Credit: Georgios Paschos PhD, Perelman School of Medicine, University of Pennsylvania)

When the clock was broken in fat cells, the hypothalamic rhythm was disrupted to favor food consumption at inappropriate times.  This means the mice would get the urge to eat in the daytime when they should be asleep.  The change in daily rhythm caused changes in metabolism.  The Penn team also found a handful of genes that were altered by the broken clock in the fat cells.  Those genes governed how unsaturated fatty acids, such as EPA and DHA were released into the blood stream.  The Penn team found that EPA and DHA levels were low at the time of inappropriate feeding.  Interestingly enough, Paschos states that the team supplemented EPA and DHA to the knockout mice, which “rescued the entire phenotype”.  The findings show that show-term changes have an immediate effect on the rhythm of eating.  These changes lead to an increase in body weight.  I really enjoyed this study.  I think it should be brought to the attention of others about the importance of not eating past a certain time.  I know there has been conflicting reports regarding nighttime eating and weight gain.  Some say it doesn’t matter when you eat, while we hear sayings like, “Eat breakfast like a king, lunch like a prince, and dinner like a pauper” all of the time.  This study seems like it supports the latter opinion.

A study done by the Early Growth Genetics Consortium, an international collaborative group, has newly identified at least two gene variants that raise the chances of common childhood obesity. Obesity is one of the largest health concerns facing modern society today and its occurrence in children is increasing. Previously studies have identified gene variants that have to do with extreme obesity, but not much is known about the genes dealing with common childhood obesity. The Center for Applied Genomics at The Children’s Hospital of Philadelphia gathered and genotyped the largest collection of DNA in the world of children with common obesity, but required help to complete its study on common childhood obesity so the Early Growth Genetics Consortium was formed.

With this help two gene loci were identified. One is near the OLFM4 gene on chromosome 13. The second gene is the HOXB5 gene located on chromosome 17. Some other evidence was also found for two more gene variants which were not specifically identified. This is also the first time that these genes were ever related to obesity. This is just the beginning of this work as the exact functions of the genes have yet to be identified, although they do lean towards having to do with the intestines. It is hoped that these findings may be able to lead to treatment or prevention of common childhood obesity based on the child’s genome.

I believe that this type of study could bring great benefit to the children affected by common childhood obesity. Obesity is one of the largest health problems in our society today and it is still growing. This study can help to take preventative measures with children who exhibit these genes and also help to treat those who are already obese with these genes before it is too late.

According to Medical News Today, at the Georgetown University Medical Center researcher identified gene called BDNF which mutation cause obesity in human being. A studied on mice proved that a mutation causes failure of neurons to stop passing chemical signals which helps hunger to suppress. The importance of the bdnf (brain-derived neurotropic factor) is forming synapses which cause neurons to sends chemical signals to other neurons. However, Bdnf controls the leptin and insulin signals by brain neurons. Uncertainty, hormones do not affect the correct location in the hypothalamus when person eat, person would not stop eating.  

     A studied was proved by using two mice groups. A mouse has a gene mutation on Bdnf gene and the other with normal gene. Researchers measure the food consummation or body weight and the increases of obesity among mouse. Based on the study result was that the mutated mice body weight increased and mice became obese; while non-mutated gene mice does not showed any changes.  They said that if leptin does not trigger in the mutated mice; than the hypothalamus would not activate as if in non-mutated mice. A researcher believes that drug could be used to encourage the bdnf or “adeno-associated virus-base gene therapy”.  

    Overall, it is great that researcher find gene mutation of bdnf that is inked to obesity. In future, this gene mutation might be a big problem for obesity if it will not be identified.  Also, over weighted person could control their diet or do exercise daily  to prevent from obesity.

Researchers are suggesting that those who have inherited obesity genes, may be more likely to become obese if they drink a large amount of sugary beverages. To come to this conclusion, scientists analyzed the genetic profiles of 33,000 men and women. According to Lu Qi, assistant professor in the nutrition department at the Harvard School of Public Health, “The risk of becoming obese as a result of carrying a high dose of obesity genes was more than twice as great in the group with the highest intake of sugary beverages as it was for the lowest intake group.” Basically, high consumption of sugary drinks greatly increased the genetic risk of becoming obese. (It is worth noting that health, exercise level, and eating habits were taken into consideration.) The results of this study will be published in the New England Journal of Medicine on September 21, 2012.

I would think that sugary drinks put everyone at a higher risk for obesity, whether they carry obesity genes or not. I would like to know how they can determine when obesity is caused by genetics along with sugary drinks rather than just the genetics alone. Either way, it is nice to know that those who are genetically predisposed to obesity can lessen their chance of becoming obese by living a healthy lifestyle.

Researchers at UT Southwestern Medical Center have genetically altered mice in a way that their bodies will metabolize excess energy and have lower levels of obesity, despite a caloric surplus.  The mice were modified to produce a larger amount of MED13, a chemical that affects thyroid function.  Mice with the elevated levels were much leaner than their normal counterparts.  In contrast, another group of mice had the MED13 gene deleted.  These mice had a much higher level of bodyfat and stored a much greater amount of excess energy.  The results of this experiment were not exactly surprising since we already have the knowledge concerning how thyroid function affects energy storage and other factors such as insulin sensitivity that often lead to obesity.  The reason it is significant is that the researchers used genetic modification rather than drugs to manipulate metabolism.