Locking up Fats in CAGEs to Treat Obesity

A review of:

Brownell, Lindsay. “Locking up Fats in CAGEs to Treat Obesity.” Wyss Institute for Biologically Inspired Engineering, 26 Nov. 2019, wyss.harvard.edu/news/locking-up-fats-in-cages-to-treat-obesity/.

In “Locking up Fats in CAGEs to Treat Obesity” Lindsay Brownell described a new study from Harvard’s Wyss Institute for Biologically Inspired Engineering and John A. Paulson School for Engineering and Applied Sciences (SEAS). The study found that if Choline and Geranate (CAGE) is orally administered, it can physically reduce the absorption of fats from food. CAGE is a liquid salt that was originally created several years ago by Samir Mitragotri as part of an effort to improve medicine absorption by the human body. During that study, it became clear that the uptake of small hydrophobic molecules was not aided by CAGE. The researchers of the study suspected that CAGE was somehow binding to those molecules and preventing them from getting absorbed. “That observation led us to wonder if there were any contexts in which we would want to prevent the uptake of this type of molecule. We realized that fats are small and hydrophobic, and that CAGE could potentially be of interest as a medical treatment for obesity,” said Mitragotri, who is also a professor of bioengineering. The team first tested the impacts of CAGE on fats by mixing it with DHA, an omega-3 fat and water. They then tested the DHA-CAGE solution to healthy rat intestines ex vivo, before moving on to testing CAGE in living organisms. Capsules containing the DHA-CAGE solution was orally fed to living rats. After six hours, the researchers found that only half of the DHA was absorbed into the bloodstream, as compared to when the rats were fed DHA alone. Further tests were performed on the rats, and Mitragotri’s team learned that rats gained 12% less weight on a high fat diet with CAGE than rats on the same diet that were not given CAGE. Most importantly, during the month-long tests with CAGE, there were no side effects observed in the treated rats - no signs of inflammation and no changes in organ structure or function.

This research has the potential to be developed further and to help many people struggling with weight issues. Over one third of American adults are affected by obesity, a condition which also increases the risk of other diseases - high blood pressure, diabetes, asthma, to name a few - which can often be fatal. Obesity is a growing epidemic, and is one of the most significant public health threats. The cost of treating obesity and obesity-related diseases is expected to double every decade. Further testing with CAGE may lead to a widespread solution that would help with the epidemic. “This is the first proof-of-concept that orally administered ionic liquids can help reduce fat uptake and body mass, and this approach has significant clinical potential given that it is simple, fast, and much less invasive than liposuction or bariatric surgery and, because its mechanism of action is physical rather than chemical, it lacks the side effects observed with other drugs,” said Mitragotri.

Brownell’s article was well written, informative, and impactful - a necessary combination for exposure. The article was interesting, and structured in a way that holds a reader’s attention. It’s only weakness was a lack of the researcher’s actual data. There were no data tables or images of the experimental setup, nor images of the proposed molecular molecular bonding between CAGE and fat molecules. Brownell’s article shared the researchers’ sentiments with the readers, a move that also keeps readers aware of the researchers’ intentions and makes the article more powerful. “Our goal is to translate this work into a product that can help people maintain a healthier weight, and this study marks the very beginning of that journey”(M.D. Nurrunabi).

Rachel Roberts

12/12/19

Sanders, Laura. “A Once-Scrapped Alzheimer's Drug May Work after All.” Science News, 6 

Dec. 2019, 

www.sciencenews.org/article/once-scrapped-alzheimers-drug-aducanumab-may-work-after-all.

In the article, “A Once-Scrapped Alzheimer’s Drug May Work after All,” Laura Sanders discusses how aducanumab, a drug designed to slow the progression of Alzheimer’s, could be effective even though it had shown not to be promising in its testing stages. However, when looking more at the data from the trials, it showed that “People who took the highest amounts of the drug declined about 30 percent less, as measured by a commonly used Alzheimer’s scale than people who took a placebo, Samantha Haeberlein of the biotechnology company Biogen reported at the Clinical Trials on Alzheimer’s Disease meeting in San Diego.” Aducanumab is an antibody that is designed to target amyloid, a protein that is believed to be one of the early steps of the disease. While the drug did remove the amyloid from patients’ brains, it did not seem to slow the symptoms a more significant amount than those on a placebo treatment. However, once the data collected after the initial analyses were available, it became clear that those on the highest dose showed signs of their symptoms slowing down. “Updated results included a total of 3,285 people who had early signs of cognitive slipping. Surveys measured participants’ abilities in six aspects of life, including memory, orientation, personal care, and problem-solving. Analyses on a subset of 288 people in one trial who received the highest dose showed that, while they still lost some mental abilities over the year and a half of the study, they declined 30 percent less than those who received the placebo. A similar subset of 282 people in the other trial declined 27 percent less than those who took a placebo. Brain scans showed that, compared with people on the placebo, the brains of people taking aducanumab had less amyloid — and less tau, another protein associated with Alzheimer’s.” These results may seem encouraging the drug being successful. However, many scientists are still wary of possible side effects such as swelling of the brain so, aducanumab may not be available until it is deemed completely safe. 

Aducanumab would be completely life-changing once available to the public. Currently, Alzheimer’s medications can only temporarily hold off symptoms and cannot resist the destruction of the brain. Rebecca Edelmayer, director of scientific engagement for the Alzheimer’s Association in Chicago, said, “A treatment that could actually slow or even stop the damage would have a huge impact for patients and their caregivers,” she says.” Also, the results of these trials could help prove that the protein amyloid is not a red herring but a critical early step of Alzheimer’s. This would be very helpful when trying to create new medications for the disease. Also, some of the brain scans from the tests showed that the people taking aducanumab had less tau, which is another protein associated with Alzheimer’s. These results could also help as they would show how and if the disease was slowing down. This would allow doctors to track the damage the disease does to patients and would maybe help them find ways to stop its effects altogether. Lastly, Sharon Cohen, a behavioral neurologist at the Toronto Memory Program, said during a panel discussion at the meeting, “Those of us who know this disease will know what it means to lose yourself slice by slice. Anything you can hang onto, and do well, is a triumph.”

When reading the article by Laura Sanders, there were many good aspects of her writing. 

She explained the information in the article very well. I was able to understand it even though I have no previous knowledge of the topic. Also, she integrated the story of proving aducanumab is effective in her article while also giving the main details of the research. This allowed me to get a full picture of how important this topic was and how it could affect research, especially in neurology and drug tests in the future. While Sanders did an excellent job explaining the research and the story, the article itself could be choppy. There were areas in the article where the focus of the paragraph would flip between two subjects. It often confused me as I wouldn’t know what was being mentioned at the moment. It would be much better if each paragraph had its focus, so there could not be any confusion on the topics. Lastly, while her article was grammatically correct, there were several areas where it was very wordy and made me go back and read the sentence multiple times. For example, Sanders wrote, “ After being shelved earlier this year for lackluster preliminary results, a drug designed to slow Alzheimer’s progression is showing new signs of life.” When writing articles for a website that is open for anybody of any career or interest to look at, it is much better to stay with more simple syntax and grammar so more people would be able to understand fully. 

Ellyn Paris 12/12/19

AP Biology Current Event 11

Fritts, Rachel. “Power Lines May Mess with Honeybees' Behavior and Ability to Learn.” Science News, 14 Nov. 2019, www.sciencenews.org/article/power-lines-may-mess-with-honeybees-learning-behavior.

In her article, Rachel Fritts discusses the issues bees are facing in regards to power lines. She begins by citing a study that exposed a group of bees to EMFs (electromagnetic fields), the fields that power lines emit. Sebastian Shepherd, an entomologist that partook in this study, found that the exposed subjects were “aggressive towards other bees” (Fritts, 1) and “slower to learn to respond to a new threat” (Fritts,1). These findings were connected to the recent loss of honeybee colonies. Scientists have found that a multitude of reasons are causing this species to decrease in quantity, and powerlines are one of the stressors that play a role in weakening bees are lowering their survival rate. Fritts cites another study in which bees were exposed to EMFs at different levels (measured in microteslas) for different lengths of time. The results were as expected: a bee’s capabilities and time of reaction when in a threatening position was altered negatively when the bees were exposed to high amounts of EMFs for a long time. In the end, the author touches upon the possible solutions, including an ecologist named Kimberly Russell’s idea of providing fields of accessible wildflowers to bees to reduce the stress put on them.

Bees are a crucial part of many ecosystems. The pollination services they provide are necessary to upkeep the health of our environment. Furthermore, as the article mentions, these insects provide “$15 billion in annual agricultural value” (Fritts, 1). Consequently, the state of their species’ wellbeing is more than important. The fact that honeybee colonies are seemingly disappearing is concerning and foreshadows a bleak future for our planet, as well as our agricultural market. Power lines are located almost everywhere in the United States. EMFs are not something that bees can avoid, therefore solutions such as the one Russell suggested are principal in conserving the existence of honeybees, and as a result, the welfare of our ecosystems. 

The article’s main strength was its use of studies to back up the conclusions being made. The author cited the people working on these studies and clearly outlined what each study was about and the findings that resulted from them. However, Fritts did not mention the importance of bees in an ecosystem. I believe to improve her article, the author should discuss the significance of bees. This would allow her to captivate the reader’s attention and make them realize the severity of the issues being discussed.

Caroline McGrath

12/04/19

Hunt, Katie. “Climate Change Could Be Making Birds Shrink in Size, Study Finds.” CNN, Cable 

News Network, 4 Dec. 2019, 

www.cnn.com/2019/12/04/world/dead-birds-body-size-climate-change-scn/index.html. 

41 years ago, Dave Willard began collecting bird corpses he found on the street simply for the reason “Why let them go to waste.'' After collecting the birds, some days over 300 birds, he goes home and measures them. Now, I have no idea why one would ever feel the need to measure dead birds, but alas Willard’s ‘hobby’ made a discovery of the first of its kind; simply this: birds are shrinking. The birds he collects are flying from Canada to Latin American in time for winter, and often find themselves crashing into skyscrapers and falling to their deaths, when Willard picks them up. Willard has been doing this since 1978 and collected over 100,000 dead birds, and noticed a particular pattern in the size measurements: the torso is shrinking, and the wings are getting longer. Willard and his team have credited global warming to this trend. Because the temperature has risen in the north, birds have adapted smaller bodies, as there is less need for larger bodies to contain heat and to compensate for the smaller body, the wings have grown. Out of 52 species collected, 49 have shown an average of 2.4% decrease in body size and 1.3% growth in wingspan.

This adaption could have many implications on our society. What is it’s not just with birds? What if Willard was lucky to catch these findings because animals all around are growing and shrinking and we don’t notice? Our entire animal kingdom could be different in twenty years because of global warming. Climate change is talked about a lot, but this is a new consequence in the developing phase, but could be threatening to our species. 

I believe the article was very well done, especially the title which immediately grabbed my attention and made me want to read more. I do think that the article lacked some explanation. It stated things like “ bird's wingspans may have increased to compensate for smaller bodies that produce less energy for the incredibly long distances the birds travel during their migrations.” I would have said a smaller body had the opposite effect on the wingspan, and was shocked to read this, however, I found no explanation whatsoever over why this was the case. I think in order to improve this article, there needed to be more of a why not so much as a how. I understand that it is shrinking and growing, but after reading I was still unsure of why.

Lily Jebejian

O'Connor, Anahad. “Fake Meat vs. Real Meat.” The New York Times, The New York Times, 3 Dec. 2019, www.nytimes.com/2019/12/03/well/eat/fake-meat-vs-real-meat.html.

The article “Fake Meat vs Real Meat”, by Anahad O'Connor, explores the new phenomenon of plant based meat. Recently many companies, such as “Beyond” or “Impossible” have begun to produce products designed to look and taste like meat, but they are actually made completely from plants. There has been a lot of controversy surrounding these new products. Many claim that the plant-based burgers are a healthier option compared to regular hamburgers, while others say that the fake burgers are even more fattening than the original. This article compared both sides of the argument. The impossible burger is said to smell, taste, and even bleed like real meat, but is completely made of plants, “The Beyond Burger has about 18 ingredients, including purified pea protein, coconut and canola oils, rice protein, potato starch and beet juice extract for coloring”(O’Connor). The reduction of consuming meat (specifically beef) has its benefits. Besides being cutting down on red meat for dietary reasons, consuming less cows will help the environment as well by reducing on green house gas emissions. But many studies have found that the processing required to create the burgers makes them the same or even more fattening, “...fake meats as ultra-processed foods that can spur weight gain”(O’Connor). This article really made me consider the meat I eat and how I can limit it in my diet for many reasons. 

This article is very important to society because it has an impact on health and the environment. It can be very influential in people’s dietary needs, by allowing people to cut out red meat while still enjoying the taste. In addition, by cutting down on the amount of cattle we can reduce the emission of green house gases into the atmosphere. This will also allow for the preservation of land that would otherwise be used to raise livestock.

I learned a lot from this article and think it is a very interesting solution to the global crisis occurring now. With this simple swap we can help save the planet while still enjoying the same food as before. I do think a lot more research needs to be done about the exact impact this dietary change will have on humans. There may also need to be improved recipes, but over time I think this option is a very realistic one that can make a dramatic change.  

Little-known protein appears to play important role in obesity and metabolic disease

Ava Chiang 

11/24/19

AP Biology

Current Event #9

Scripps Research Institute. "Little-known protein appears to play important role in obesity and metabolic disease: The recently discovered protein is normally abundant in fat; without it, the body struggles to manage glucose and insulin." ScienceDaily. ScienceDaily, 20 November 2019. <www.sciencedaily.com/releases/2019/11/191120175618.htm>. 

In the article “Little-known protein appears to play important role in obesity and metabolic disease” published by the Scripps Research Institute, scientists discover a protein that is highly expressed in fat tissue. This discovery leads to new discoveries about obesity and metabolism, and may introduce new ways for addressing obesity related illnesses. This new protein is called PGRMC2 and had been detected in the uterus, liver, and other areas of the body. PGRMC2 is important because it encapsulates a molecule called heme, and transports it from the cell’s mitochondria to the nucleus, without this protective barrier PGRMC2 provides, heme would react with and destroy everything in its path. Heme is an iron containing molecule that travels within the cell to enable crucial processes such as cellular respiration, cell proliferation, cell death, and circadian rhythms. Enrique Saez, PhD, and his team centered their research around “what happens in the body if this protein doesn't exist to transport heme.” They discovered that wihtout PGRMC2 present in fat tissues, mice fed a high-fat diet became intolerant to glucose and insensitive to insulin, while obese-diabetic mice treated with a drug that activates their PGRMC2 levels show improvement with their symptoms. PGRMC2 levels are also high within brown fats, known as the good fats. A key role of brown fat is to generate heat to maintain body temperature, without PGRMC2, heme cannot function, and body temperature drops due to mitochondrial dysfunction.

Diabetes and other obesity related metabolic diseases are one of the most costly illnesses in the world, and its numbers are fast rising. In America alone, adult obesity rates exceed 35% in nine states. 30% in 31 states, and 25% in 48 states. The discovery of PGRMC2 can introduce a new way to reduce deaths caused by obesity and also improve the symptoms of it. The lack of PGRMC2 combined with a high-fat diet in mice shows the symptoms of diabetes, therefore, the addition of PGRMC2 could be the key to curing obesity. In addition, the protein (PGRMC2)  that helps transport heme, a molecule known to react and destroy anything in its path, had not been identified until now. So regardless of the future uses of PGRMC2, it is still a great scientific discovery.

This article was very interesting and informative, it included quotes from the leading scientists of this research and also explained the significance of this protein in detail. In addition, multiple examples of the types of experiments using PGRMC2 were provided. However, this article went straight into the deep end with this information, I felt like it would be more helpful to introduce the protein mentioned in this article, PGRMC2, by first talking about how it was discovered. In addition, there is no information in this article about when this discovery would be able to be used on humans, or if there were any negative effects on the mice from the drugs that increase PGRMC2 levels. If possible, I would like to see the author include more background information in the article.

“California Landfills Are Belching High Levels of Climate-Warming Methane.”

Olivia Conniff

Mr. Ippolito

Current Event 9

11/24/19

Gramling, Carolyn. “California Landfills Are Belching High Levels of Climate-Warming Methane.” Science News, 13 Nov. 2019, www.sciencenews.org/article/california-landfills-are-belching-high-levels-climate-warming-methane.

For my ninth current event, I decided to read “California Landfills are Belching High Levels of Climate-Warming Methane” by Carolyn Gramling. In her article, Gramling gives the details of the efforts of a group of researchers who used airborne remote sensing to find the exact places in California, that produce the greatest amount of methane, one of the most potent greenhouse gases. These researchers discovered that the greatest producers of methane are dairy farms, the oil and gas industry, and the highest producer being landfills. It was discovered that landfills contribute 41% of methane emissions, and dairy farms and the oil and gas industry contribute 26% each. 

This research on the greatest sources of methane production is extremely important, as it means that we can focus our mitigation efforts on those sources, to slow the rate of climate change and stop this gas from deteriorating the ozone layer. It will help us to zero in our efforts on facilities that are producing the greatest amount of greenhouse gases, particularly methane.

While I found Gramling’s article to be very interesting, it was a bit confusing while reading, and I certainly had to go back multiple times and reread. It started out strong and clear, talking about the team of researchers focused on pinpointing the greatest producer of methane in California. It was also very clear when giving facts and statistics, particularly the percentages that make up the greatest producers of methane. However later in the article it got confusing when describing 5 different research efforts at once. It was worded strangely and very hard to follow. I feel she could have improved this if she had focused on each research effort separately or not included so many. However, overall it was a very interesting and informative article.