Adiposity: Relevant, Polemical and Urgent Problem

Obesity is one of the most widespread health problems in the United States. Approximately two-thirds of Americans are either already obese or approaching that designation. While the term “obesity” is often misused as a synonym for “fat,” its scientific definition demonstrates how serious obesity is and how difficult it can be to control. Doctors identify obesity as when an individual’s body mass index (BMI) is over 30, or when they are 20% heavier than their ideal body weight. Those who are obese suffer from an abnormal accumulation of fat throughout their body and thus become more susceptible to a host of chronic diseases.

Obesity not only affects people’s quality of life but also has broad social, medical, and economic costs. My scientific technology will address obesity’s underlying causes, mitigating the long-term harm it does to individuals and the burden it places on the national health care system.

Obesity contributes to seven of the top ten causes of death in America.

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It has been implicated in a range of conditions, from cancer, hypertension, heart disease, and stroke, to diabetes, and emotional and psychological problems. The obesity epidemic is only getting worse. In 1986, 1 in 200 Americans was morbidly obese. Today, that number has increased by a factor of 40, with one in five American adults suffering from morbid obesity. It is predicted that 60% of males and 50% of females will be obese by 2050. According to a recent study conducted by researchers at Oxford University, moderate obesity has been found to reduce life expectancies by three years.

Obesity is believed to contribute to the deaths of over 300,000 people each year, and will likely “supersede tobacco” as the biggest cause of premature death by 2050.

In addition to the considerable medical burdens obesity incurs, it also has alarming economic and social consequences. The United States healthcare system spent $147 billion to address things eating direct medical costs of obesity in 2008 alone. In addition to these direct costs, the indirect costs of “absenteeism” and “presenteeism” from obesity-related health problems are estimated to run between $3.4 and $6.4 billion a year, or roughly $106 per obese person. In addition to the quantifiable economic and medical burdens of obesity, such as human and financial loss, the social burden is immeasurable. Obesity leads to decreased quality of life, disproportionately affects the poor, and reduces military eligibility. Disabilities, handicaps, and depression rates all rise in tandem with obesity rates. Obese people are three to four times more likely to be depressed, and obese women are 37% more likely to commit suicide. Conventional wisdom holds that depression leads to binge eating and therefore obesity, but scientific research has found that obesity is more often a precursor to depression. Professor Hubert Lacey of the Royal College of Psychiatrists affirmed that “obesity causes depression rather than depression causing obesity.” In addition to high depression rates, obesity triggers other social problems. The biggest is obesity’s outsized effect on the poor. Because lower-income households have more difficulty affording and sourcing nutritious food, have less time to exercise, incur higher stress levels and live in worse conditions, the poor are more likely to be obese. It is estimated that “33 percent of adults who earn less than $15,000 per year are obese, compared with 24.6 percent of those who earned at least $50,000 per year.” One-third of adults who did not graduate from high school are obese, whereas one-fifth (21.5%) of college graduates are obese.

My new scientific technology will be a pill. Assuming unlimited resources are available to create and perfect this pill, it will not require a cold chain or a significant behavioral change. This enables the pill to be distributed as widely as possible since it can be easily transported and administered. The pill will be small and efficiently packed, meaning a dose will only be required monthly. This means people will not have to adhere to a strict daily regimen. The contents of the pill will enable the stronger promotion and enhancement of the genes PRDM16, ADIPOQ, LEP, and the protein LEAP2 in transcription/translation toward increased protein expression.

Years of scientific research and data analysis have yielded a deep understanding of obesity and its driving factors: genetics, diet, physical activity, and type of fat. Scientists have studied, tested, and discovered which chronic illnesses obesity contributes to, along with what driving factor is associated with each chronic disease. One of the most unhealthy aspects of obesity is visceral fat, which is deposited around the organs. An excess of visceral fat can cause insulin resistance, diabetes, heart disease, and inflammation. Visceral fat is not usually visible to the naked eye, making it easy to overlook. This fall, I had the opportunity to visit Dr. Paul Cohen’s Molecular Metabolism lab at Rockefeller University, where I was exposed to their outstanding work on adipose tissues and their genetic makeup. Inspired by this visit, I have created a scientific technology directed toward regulating levels of visceral fat, subcutaneous fat, and three hormones (leptin, ghrelin, adiponectin)and t, through gene enhancement and protein expression.

At the Cohen lab, I witnessed exciting research on adipocytes in mice. Adipocytes are specialized cells that store fat and are found in connective tissue. They come in several distinct types, including beige, white, and brown. The study of adipocytes is constantly evolving, as scientists continue to understand the role they play in influencing obesity. One thing scientists know for certain is that white adipocytes are associated with the storage of fat and are “marked by inflammation and an increased accumulation of immune cells” in obesity. Beige fat cells, however, have been found to dissipate, or burn, energy when activated. Beige fat cells are associated with subcutaneous fat and can have “neutral or even beneficial” effects for the obese. Typically, people who have more subcutaneous fat than visceral fat are healthier, and their bodies are more resistant to weight gain. It is the increased amount of visceral fat that leads to “obesity, insulin resistance, and fatty liver.” An increase in beige fat, which has been found to burn energy by uncoupling the mitochondrial proton gradient in ATP synthesis, can help suppress a crucial prerequisite to obesity. This is where PRDM16 comes into play.

At Rockefeller University, Dr. Cohen and his colleagues discovered that PRDM16, a protein that helps regulate gene expression, acts “as a molecular switch” between important components of visceral and subcutaneous fat. Essentially, it can control the level of visceral fat and determine whether millions of Americans become obese or remain healthy. It does so by activating beige adipocytes rather than white adipocytes, burning calories instead of storing them. When scientists at Rockefeller erased the PRDM16 gene in mice, “beige adipocytes no longer functioned properly,” and the mice became obese. This is why a pill enabling the increased expression of the protein PRDM16 will greatly help people on the brink of obesity. This protein activates beige adipocytes and ensures they function properly. I aim to put the protein in “hyperdrive,” increasing the number of beige fat cells in obese people, causing them to burn more energy and lose weight.

The second important hormone the pill will aim to increase is adiponectin. Adiponectin modulates “the metabolism of lipids and glucose,” meaning it preserves healthy levels of insulin sensitivity. In leaner subjects, adiponectin levels are higher than in obese subjects. When levels of our bodies’ “regulator” are low, so are our insulin levels, making people more susceptible to diabetes and obesity. The ADIPOQ gene encodes Adiponectin. As with PRDM16 and beige adipocytes, the pill will enhance the sequencing of the ADIPOQ gene in transcription in order to increase adiponectin levels and insulin sensitivity.

The final hormones the pill will focus on are leptin and ghrelin. Dubbed the “hunger hormones,” leptin and ghrelin regulate feelings of satiety and hunger in our bodies. Leptin’s role is to reduce food intake and body weight, explaining why leptin levels rise with weight gain and fall with weight loss. This only occurs when the leptin receptor is functioning properly. When someone is obese, they are much more susceptible to contracting a condition known as “leptin resistance.” When leptin resistance occurs, obese subjects have too much leptin in their bloodstream and thus their body does not respond to the signals for reduced food intake. By manipulating the levels of LEP, the gene that codes for leptin in transcription and translation, the pill can increase the level of hunger stagnation in the body, reducing unhealthy eating practices.

Ghrelin, on the other hand, stimulates the secretion of growth hormone and increases appetite. German scientists believe ghrelin plays a significant role in how frequently we eat, since ghrelin levels change drastically depending on the last time we ate. Until recently, however, there was no known way of regulating the ghrelin system. That all changed about two years agotoaffect when researchers at GM Biopharmaceuticals discovered that a protein called “LEAP2” inhibits “the receptor for ghrelin by fastening to it and possibly preventing ghrelin from latching on.” By conducting several tests on mice, scientists concluded that LEAP2 is “a new, important part of the ghrelin system.” Bariatric physician Carel le Roux pointed out that it could help fight obesity by preventing “that almost inevitable hunger that follows weight loss.” For these reasons, my pill will contain strands of the promising protein LEAP2, in order to decrease the level of ghrelin in obese subjects.

Research shows that obesity is strongly linked to certain genes and their expressions, rather than character habits or behavioral patterns. Gene manipulation, rather than an increase in exercise or a diet change, has the most potential for having a significant mitigatory effect on obesity. Gene manipulation also does not require major behavioral changes, since you only need to take the pill once a month. Behavioral changes are unlikely to take place and even unlikelier to stick. For these reasons, the pill addresses the internal makeup and genetic code of humans, attacking obesity at its root causes. Another advantage of the pill is the ease with which it can be distributed and consumed. The pill is not a boutique drug, because obesity tends to disproportionately affects the poor. By bringing an inexpensive, convenient solution to market, the pill can help victims of obesity who need it most, the poor. Because this solution is simple, elegant, ago affect, and easy, it can be shipped to patients in low-income countries where it can have an overwhelming impact. Ultimately, regardless of the demographic that an obese person belongs to, this pill will provide them with an opportunity to live a longer and healthier life.