© ISTOCK.COM/PACI77Between October 2013 and July 2014, six healthy, middle-aged men reported to Temple University Hospital in north Philadelphia. For seven days, researchers confined each subject to his hospital bed and told him to select breakfast, lunch, and dinner, along with three daily snacks, from the hospital menu containing typical American cuisine: eggs, fried chicken, hamburgers, French fries, etc. The intake totaled a whopping 6,000 calories—about 2.5 times the men’s normal diet.
Physician Guenther Boden of the Temple University School of Medicine and his colleagues had recruited the men to investigate how overeating leads to insulin resistance, which in rodent models happens quickly and dramatically, well before the animals gain much weight. Researchers had proposed several possible mechanisms, including elevated levels of fatty acids; inflammation; endoplasmic reticulum (ER) stress; and oxidative stress. “If you look at people who are obese and insulin resistant, you find all sorts of abnormalities that could explain the insulin resistance,” says Boden. “What no one knows is how the whole thing starts.”
Every day, the researchers weighed the men and drew their blood; before and after the week-long binge, they biopsied fat tissue from the participants’ thighs. Then, the research team analyzed ...
