{"id":6653,"date":"2012-03-13T15:15:19","date_gmt":"2012-03-13T19:15:19","guid":{"rendered":"http:\/\/www.bumc.bu.edu\/busm-news\/?p=2146"},"modified":"2012-03-13T15:15:19","modified_gmt":"2012-03-13T19:15:19","slug":"why-we-are-fat-busm-biochemist-says-chemicals-not-just-calories-could-explain-epidemic","status":"publish","type":"post","link":"https:\/\/www.bumc.bu.edu\/camed\/2012\/03\/13\/why-we-are-fat-busm-biochemist-says-chemicals-not-just-calories-could-explain-epidemic\/","title":{"rendered":"Why We Are Fat: BUSM Biochemist Says Chemicals, Not Just Calories Could Explain Epidemic"},"content":{"rendered":"
\"\u201cBarbara<\/a>
\u201cBarbara Corkey is one of the few people who really understand and integrate metabolism into diabetes research,\u201d says Ronald Kahn, past president of the Joslin Diabetes Center. \u201cFor the last 30 years, metabolism has been a lost science. She helped keep the field alive.\u201d Photos by Vernon Doucette<\/figcaption><\/figure>\n

We all know why Americans are fat, right? We gobble chips and chug 16-ounce sodas and then park our butts in front of the TV. Seems pretty straightforward. But what if that\u2019s not the whole story? Biochemist Barbara Corkey has an idea that turns this conventional wisdom on its head.<\/p>\n

What if, asks Corkey, obesity isn\u2019t simply about eating too much and exercising too little? What if there\u2019s something more subtle at work? Maybe it isn\u2019t extra calories that make us fat, she says, but food additives like saccharin and emulsifiers.<\/p>\n

\u201cI don\u2019t believe that overeating causes obesity,\u201d says Corkey flatly. \u201cDuring my lifetime I have seen tremendous differences in food preparation and food packaging\u2026.When that novelty is associated with an increase in obesity and diabetes, is it rocket science to ask whether these things are related?\u201d<\/p>\n

Corkey\u2019s suspected connection may seem like a stretch, but she is not one to oversimplify science. She is a respected scientist with five decades of metabolism research under her belt. She\u2019s the vice chair of research at the School of Medicine department of medicine, and in November was appointed MED\u2019s Zoltan Kohn Professor in Medicine<\/a>. She\u2019s the former director of the Obesity Research Center at Boston Medical Center and recent past editor of the medical journal Obesity<\/a><\/em>, and last year she was awarded the Banting Medal for Scientific Achievement Award<\/a>, the American Diabetes Association\u2019s highest scientific honor and one of the world\u2019s top science awards.<\/p>\n

\u201cBarbara is out of the box\u2014completely,\u201d says collaborator Orian Shirihai, a MED associate professor of medicine. \u201cShe doesn\u2019t even know what\u2019s in the box. What she does is turn the box upside down and put it onto other scientists\u2019 heads.\u201d<\/p>\n

Corkey\u2019s area of expertise is metabolism: she studies how cells, specifically cells involved in diabetes and obesity, communicate. \u201cMetabolic disease has always interested me,\u201d she says. \u201cIt\u2019s a system where pathways all interconnect and talk to each other. And so if you push on one button over here, it has consequences everywhere else.\u201d<\/p>\n

A key player in her research is the pancreatic beta cell, which produces insulin, a hormone that converts food into energy and stores it as either fat or glucose. In diabetics, the beta cells usually produce too much, too little, or no insulin. The reasons for beta cell breakdown are complicated, and that\u2019s what attracts Corkey.<\/p>\n

\u201cBarbara is one of the few people who really understand and integrate metabolism into diabetes research,\u201d says Ronald Kahn, past president of the Joslin Diabetes Center<\/a> and a professor of medicine at Harvard Medical School. \u201cMetabolism is coming back now, but for the last 30 years it has been a lost science.\u201d Kahn, who calls Corkey \u201cthe queen of metabolism,\u201d says that \u201cshe helped keep the field alive.\u201d\"Corkey<\/a><\/p>\n

Click here<\/a> to view a diagram of how additives lead to diabetes, based on Barbara Corkey’s research. Diagram by Ed Wiederer<\/p>\n

Fortuitously, it turns out. Diabetes now threatens to become a worldwide epidemic. According to the U.S. Centers for Disease Control and Prevention<\/a> (CDC), 25.8 million children and adults in the United States\u20148.3 percent of the population\u2014have the disease, which is the leading cause of kidney failure and blindness among adults. If current trends continue, a third of U.S. adults could have diabetes by 2050. Outside the United States, the numbers are equally grim. According to the World Health Organization<\/a> (WHO), 346 million people worldwide\u20145 percent of all humans\u2014have diabetes, and diabetes deaths will likely double by 2030.<\/p>\n

Decades ago, when the disease was not well understood, scientists knew that two types of diabetes existed\u2014type 1 and type 2\u2014but they didn\u2019t have a clear picture of the underlying causes. People with type 1 diabetes, which is usually diagnosed in children, cannot produce insulin and must inject it to survive. Scientists thought that type 2 diabetics, who are usually adults and often obese, had a less dramatic deficit: some insulin but not enough. But when scientists came up with a way to measure insulin levels, they found that people with type 2 diabetes actually had too much insulin.<\/p>\n

If they had plenty of insulin, what caused the diabetes? The researchers theorized that insulin receptors in the muscle and fat tissue, bombarded by an excess of the hormone, became desensitized and didn\u2019t work as they should. This \u201cinsulin resistance\u201d causes the beta cell to crank out more insulin, and sometimes to stop working altogether. By the 1980s, the idea that insulin resistance alone causes type 2 diabetes had solidified into scientific dogma.<\/p>\n

There was only one catch: nobody knew which came first, the broken beta cells or the insulin resistance. Corkey was determined to find out. \u201cI think perversely,\u201d she says. \u201cWhy is the beta cell secreting more insulin? The glucose isn\u2019t elevated. How can we explain this?\u201d She suspected that the beta cells were partly responsible for triggering diabetes. And she spent the next two decades trying to prove it.<\/p>\n

The role of outsider suits her. \u201cI like to be in a comfortable place where we don\u2019t have to compete and rush, and we can do our science in a thoughtful and leisurely manner,\u201d she says. By all accounts Corkey also enjoys the role of scientific gadfly.<\/p>\n

\u201cShe likes to be provocative,\u201d says Sarah Krawczyk (MED\u201911), one of Corkey\u2019s postdoctoral students. \u201cLots of her theories challenge dogma, though they\u2019re always backed up by sound science.\u201d For two decades, while insulin resistance dominated diabetes research in the United States, Corkey stuck stubbornly with the beta cell theory. \u201cI just thought the whole United States was wrong,\u201d she says.<\/p>\n

She was right. Scientists now widely accept that a person can\u2019t get type 2 diabetes without malfunctioning beta cells, a paradigm shift largely precipitated by Corkey.<\/p>\n

\u201cShe just really changed that field and put metabolism into it, and she\u2019s basically regarded as the expert,\u201d says Susan K. Fried, a MED professor of endocrinology, diabetes, and nutrition. The beta cell research, along with similar work on fat cell metabolism, helped Corkey win the 2011 Banting Medal. \u201cShe was such a perfect choice,\u201d says Kahn. \u201cShe is an excellent scientist with a huge body of work, and she has been such an important catalyst in diabetes research.\u201d<\/p>\n

Giving wing to her intellect<\/strong><\/p>\n

Watch the video<\/a> where\u00a0 biochemist Barbara Corkey explains how painting complements her work as a scientist.<\/p>\n

Corkey remembers the moment she decided to become a scientist. She was a teenager at New York University, majoring in fine arts while simultaneously pursuing an accelerated path to medical school. She loved painting, but considered it a \u201chedonistic pleasure\u201d rather than a career, and had set her sights on medicine.<\/p>\n

Walking to class one day, she glanced into a tiny lab and saw a fascinating sight: a small beating heart, dangling on a string over a dish. She stopped in her tracks. Intrigued, Corkey asked the professor why the disembodied heart was still thumping away. \u201cIt\u2019s calcium,\u201d he told her. As she watched, he changed the calcium levels in the solution. The heart stopped beating, then started again. \u201cThat\u2019s when I knew that medical school was not for me,\u201d she says. She was so smitten by biochemistry that she dropped out of NYU without finishing a bachelor\u2019s degree and joined a laboratory. That job, in 1957, marked her first foray into diabetes metabolism.<\/p>\n

From there her career followed an extraordinary path. Corkey married a Hungarian refugee at age 19 and had her first child, a son, at age 20. Her father, disapproving of the marriage and of foreigners in general, stopped speaking to his daughter. The young family moved to the University of Pennsylvania, where Corkey got a full-time job as a lab technician. After her second child was born, her husband walked out, leaving her with two small children and a mountain of debt.<\/p>\n

\u201cIt was almost impossible to live on my income,\u201d says Corkey. \u201cI couldn\u2019t afford babysitters. I couldn\u2019t afford anything.\u201d Her daughter Valerie remembers her mother struggling to provide for the family, shuttling her around on the back of a bicycle because they didn\u2019t own a car. \u201cBut I don\u2019t remember wanting for anything,\u201d she says.<\/p>\n

On the contrary, Valerie and her sister, Pamela, share happy memories of playing in their mother\u2019s lab, spinning magnets on the centrifuge and snapping tiny plastic vials together into necklaces. \u201cI wouldn\u2019t trade her for any other parent,\u201d says Valerie.<\/p>\n

While Corkey remembers those years as lonely and stressful, they shaped the woman she is today. \u201cI realized that I am in charge of me, and I\u2019m responsible for my life,\u201d she says. \u201cNo one\u2019s going to take care of me except me. And no one\u2019s going to take care of my kids except me. So get over it.\u201d<\/p>\n

Corkey dug her way out with characteristic optimism and energy. Her second husband, a medical student, encouraged her to get a PhD, and she persuaded the University of Pennsylvania to admit her without a bachelor\u2019s degree. She was awarded a doctorate in 1981, the same year her son graduated from college. She was 43 years old\u2014ancient in scientist years.<\/p>\n

\u201cIt\u2019s almost unprecedented to start a scientific career so late and achieve so much,\u201d says Richard Bergman, director of the Cedars-Sinai Diabetes and Obesity Research Institute in Los Angeles. \u201cBarbara is one of the greatest role models for women in science\u2014and for scientists in general\u2014that I know.\u201d<\/p>\n

Pamela frames her mother\u2019s accomplishments another way. \u201cHaving a bunch of kids and giving them home-cooked pot roast seven nights a week is one way to make a contribution to the world,\u201d she says. \u201cBut when your brain is capable of understanding and breaking down metabolic regulation, that\u2019s what you should be doing. I can\u2019t imagine how miserable she would have been if she hadn\u2019t given wing to her intellect.\u201d<\/p>\n

Last remaining bigotry<\/strong><\/p>\n

Corkey is now 73, and with her cropped white hair and funky earrings she looks more Greenwich Village grandma than top-tier biochemist. She radiates an aura of competence, kindness, and joie de vivre that endears her to both students and colleagues.<\/p>\n

At BU, she is known as a generous collaborator and a beloved but tough mentor. \u201cThe best mentors give you a hammer on the head and then a hug,\u201d says Shirihai. \u201cWith Barbara, you never know which it\u2019s going to be.\u201d As the department of medicine vice chair of research since 2007, Corkey helped build major research \u201ccores\u201d that allow scientists to use expensive equipment they can\u2019t afford in their own labs, such as cell imaging and high-throughput screening machines. She helped write a strategic plan for the department that included specific language to protect postdocs and junior faculty from exploitation. A gourmet cook and wine connoisseur, she encourages fraternization through food, from pairing wine and cheese for faculty gatherings to organizing an annual dim sum lunch, which draws hundreds of faculty and staff and their families.<\/p>\n

Corkey is a modest woman who avoids the limelight and disdains what she calls the \u201cbilly goats\u201d who often dominate science. She enjoys spending time alone, cherishing the quiet Friday afternoons when she can paint in her studio.<\/p>\n

\"Caption<\/a>
In her downtime, Corkey enjoys painting the Boston skyline. Her abstract works are influenced by what she sees in the laboratory and under the microscope.<\/figcaption><\/figure>\n

Krawczyk, who earned a PhD under Corkey, was unaware of her boss\u2019 status in the scientific world until they started attending conferences together and she saw other scientists treat Corkey like a superstar.<\/p>\n

As the winner of the Banting Medal, Corkey had to give an hour-long talk to a crowd of 6,000 last June, and she did not relish the prospect. Shirihai, on the other hand, looked forward to it. \u201cI wanted to see how she would use it to hammer 6,000 people simultaneously,\u201d he says. He was not disappointed. Instead of simply recapping her career, Corkey spent an hour discussing a controversial new direction for her research: whether the 4,000 additives in the U.S. food supply might be contributing to diabetes and obesity. \u201cFor those people who never got out of the box,\u201d Shirihai says with a laugh, \u201cit was like having a high-volume enema.\u201d<\/p>\n

Obesity statistics are troubling. One-third of American adults are obese, and the numbers are growing, according to the CDC, which describes the cost to the American health care system as \u201cstaggering\u201d\u2014an estimated $147 billion in 2008 dollars. And the rest of the world is catching up. According to the WHO, worldwide obesity has more than doubled since 1980.<\/p>\n

Corkey believes that extra calories alone can\u2019t possibly be causing this epidemic. \u201cThis gets to the last remaining bigotry in the world, which is against obesity,\u201d she says. \u201cIf you\u2019re a good person and you do all the right things, you\u2019re going to be lean. And if you\u2019re a bad person and you eat like a pig and you don\u2019t do any exercise, you\u2019re going to be fat. It is the only body function that we look at this way.\u201d<\/p>\n

This bigotry \u201chas slowed the field down incredibly,\u201d she says. \u201cWe don\u2019t spend enough money on research. This is the main disease that is growing the health care budget in our society, and we don\u2019t even really consider it a disease. We don\u2019t study it. We don\u2019t understand it. We have no effective treatments, because if you say, \u2018Control yourself,\u2019 and think that\u2019s an effective treatment, then you\u2019re sticking your head in the sand.\u201d<\/p>\n

Corkey is not alone in her suspicion that environmental factors may contribute to diabetes and obesity. Earlier this year, the National Toxicology Program<\/a>, part of the U.S. Department of Health and Human Services, reported that certain environmental triggers, like arsenic poisoning and some pesticides, are associated with type 1 diabetes. It also found that children of mothers who smoked during pregnancy were more likely to be obese.<\/p>\n

\u201cThere are many factors in the environment that are probably provoking this epidemic,\u201d says Harvard\u2019s Kahn. \u201cMost researchers have focused on the obvious things: you eat at McDonald\u2019s, you sit at your computer, you get fat. I think it\u2019s much more complicated than that.\u201d<\/p>\n

Many scientists and public health experts are skeptical. Nutrition expert Marion Nestle, Paulette Goddard Professor of Nutrition, Food Studies, and Public Health at New York University and coauthor of the forthcoming book Why Calories Count: From Science to Politics (ITALICS), says people are getting fatter simply because they eat too much.<\/p>\n

As for possible environmental factors, Nestle says, \u201cit\u2019s an Occam\u2019s razor situation\u2014the simplest explanation is often the one that works. I still vote for calories, but that, of course, doesn\u2019t give researchers much to do.\u201d<\/p>\n

Such criticism only galvanizes Corkey, who began her newest line of research by screening about 500 food additives for effects on liver, fat, or beta cell tissues. Two hits proved especially interesting: a class of widely used emulsifiers called monoglycerides, often found in processed baked goods, and the artificial sweetener saccharin. Both additives made beta cells secrete insulin, but not in the normal way. Usually, says Corkey, calcium is involved in stimulating beta cells to produce insulin, and when stimulated they increase their oxygen consumption. But when monoglycerides and saccharin were put to the test, neither of these things happened. Instead, the beta cells underwent some unexpected chemical changes and released molecules called reactive oxygen species, which have been implicated in cell damage, inflammation, and obesity.<\/p>\n

What do these intriguing\u2014but preliminary\u2014findings mean? At this stage, Corkey says, it\u2019s impossible to know. But she suspects that background levels of certain food additives could cause subtle but critical changes in our metabolic tissues, possibly contributing to diabetes and obesity. Many caveats remain: perhaps the additives never reach levels in the food supply that could hurt an actual human, or perhaps the cellular changes that Corkey observed are beneficial.<\/p>\n

\u201cI have a model of how things might be happening,\u201d she says. \u201cIt\u2019s a hypothesis that needs testing. And it needs to be carefully tested.\u201d<\/p>\n

While it\u2019s extremely unlikely that a single food additive could be the villain that causes obesity and diabetes, Corkey hopes to identify a handful of problem additives that could be removed from the food supply. She also knows that in the end, the additives themselves might not be the key. Rather, her research might lead to a new understanding of a metabolic pathway that could be modified to treat obesity and diabetes or to a better understanding of how individual people respond to certain chemicals.<\/p>\n

\u201cWhat I want is to find the cure, but what I don\u2019t want to do is get people all fired up in a direction that will be misleading,\u201d she says. \u201cImportant work needs to be done to prove or disprove what\u2019s right and what\u2019s wrong.\u201d<\/p>\n

Corkey\u2019s colleagues describe her as a classic biochemist. She comes up with a hypothesis, tests it, and evaluates the data. \u201cShe has a vision, she\u2019s going about it systematically, and the science will take her where it takes her,\u201d says MED\u2019s Fried. \u201cIn her mind, it\u2019s as simple as that. If we don\u2019t do the experiment and find out, we will never know.\u201d<\/p>\n

Barbara Moran (COM\u201996) is a science writer in Brookline, Mass. She can be reached through her website WrittenByBarbaraMoran.com<\/a>.<\/p>\n

This story originally ran in the winter-spring 2012 issue of Bostonia<\/a><\/em>.<\/p>\n","protected":false},"excerpt":{"rendered":"

We all know why Americans are fat, right? We gobble chips and chug 16-ounce sodas and then park our butts in front of the TV. Seems pretty straightforward. But what if that\u2019s not the whole story? Biochemist Barbara Corkey has an idea that turns this conventional wisdom on its head. What if, asks Corkey, obesity […]<\/p>\n","protected":false},"author":903,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":[],"categories":[1],"tags":[],"_links":{"self":[{"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/posts\/6653"}],"collection":[{"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/users\/903"}],"replies":[{"embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/comments?post=6653"}],"version-history":[{"count":0,"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/posts\/6653\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/media?parent=6653"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/categories?post=6653"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/tags?post=6653"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}