Our modern world is facing a two-fold crisis, although one part is not being addressed with the same rigor as the other. Undoubtedly the first part is the overarching COVID-19 pandemic which has killed 1 million people worldwide as of September 28th, 2020. Beyond this pandemic also lies a crisis that has been a silent killer for decades and is currently putting almost half of the United States population at greater risk for contracting COVID-19: the obesity crisis. It is critical that we study the mechanisms of obesity to further understand its detrimental effects, especially during a pandemic that puts obese patients at greater risk for mortality. One research lab in particular is taking great strides to uncover the neural circuit that modulates obesity-linked behaviors in humans by looking at flies.
In the article “A Leptin Analog Locally Produced in the Brain Acts via a Conserved Neural Circuit to Modulate Obesity-Linked Behaviors in Drosophila” by Dr. Jennifer Beshel and colleagues, the lab examined unpaired 1 (upd1), a mammalian leptin analog. Leptin is a fat-derived satiety factor found in humans that essentially tells the body to stop eating once it is full, often acting as the target in many obesity studies. Along with upd1, the researchers examined the domeless receptor, an analog for leptin receptors found in the human body. Studying upd1 and the domeless receptor acts as a way for the researchers to study the mechanisms of obesity in the flies and apply their findings to humans. By “knocking down” upd1 and domeless receptors (in other words, inhibiting their function) they were able to potentially model the effect of losing leptin or leptin receptors in the human body. Results showed that the upd1 and domeless receptor knockdown flies showed a heightened attraction to food cues, weight gain, and increased fat storage. Taking the experiments further, the lab also created varying food landscapes, one including the “21st century” diet as modeled by a high-fat diet. Surprisingly, both control and knockdown flies gained weight on this diet, but the knockdown flies showed a four-fold increase in weight. In summary, the article suggests the complexity of the mechanisms of obesity, showing its “heterogeneous” origin that includes both vulnerability in terms of biology as well as a changing food landscape. With a conserved neural circuit that contributes to obesity-linked behaviors found in flies, research labs like Dr. Beshel’s can help us further understand obesity in humans, which has recently been discovered to be critical in understanding the risk of the COVID-19 pandemic.
In the New York Times article “Studies Begin to Untangle Obesity’s Role in Covid-19”, journalist Katherine J. Wu explores a multitude of studies that uncover the risk of COVID-19 in obese individuals. One particular study, “Metabolic Syndrome and Viral Pathogenesis: Lessons from Influenza and Coronaviruses”, looks at how the increased levels of adipose tissue in obese patients causes leptin resistance and increases the risk of infection with COVID-19. According to the study, the accumulation of lipids found in obese individuals leads to leptin resistance which feeds forward a greater accumulation of lipids. High lipid levels in the body allows viruses to take advantage of lipid raft formation to allow easier viral entry, further up-regulating lipid metabolism and causing a chronic systemic inflammation that predisposes obese populations to more severe infections of COVID-19. Although such obesity-driven dysregulation of the immune response to COVID-19 is rapidly being uncovered, there is still much work to be done on the exact mechanisms involved. The differential progress of the disease in obese individuals is also currently posing a problem for potential vaccines, with many pharmaceutical companies claiming that they are not planning on investigating the fact that the vaccines may not even work for obese patients, sparking criticism from many medical experts. How can our nation treat COVID-19 when the vaccines are not expected to properly work in 42% of our population?
Although obesity has been a silent killer for decades, in combination with the COVID-19 pandemic, it is putting more people's lives at risk than it ever has before. It is therefore critical that researchers like Dr. Beshel continue working on uncovering the mechanisms of obesity in order to help the nation develop vaccines that will be effective in all populations, including obese patients.
Works Cited
Beshel, Jennifer, et al. “A Leptin Analog Locally Produced in the Brain Acts via a Conserved Neural Circuit to Modulate Obesity-Linked Behaviors in Drosophila.” Cell Metabolism, vol. 25, no. 1, 2017, pp. 208–217., doi:10.1016/j.cmet.2016.12.013.
Huizinga, Gabrielle P, et al. “The Collision of Meta-Inflammation and SARS-CoV-2 Pandemic Infection.” Endocrinology, vol. 161, no. 11, 2020, doi:10.1210/endocr/bqaa154.
Wu, Katherine J. “Studies Begin to Untangle Obesity's Role in Covid-19.” The New York Times, The New York Times, 29 Sept. 2020, www.nytimes.com/2020/09/29/health/covid-obesity.html?searchResultPosition=1.
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