Skinny people with obesity issue? A rare window for researchers

Claire Walker Johnson of Queens was a medical mystery. No matter how much she ate, she never gained weight.

And yet Johnson, with a long narrow face, had the conditions many obese people develop — Type 2 diabetes, high blood pressure, high cholesterol and a liver buried in fat.

She and a very small group of very thin people like her have given scientists surprising clues to one of the most important questions about obesity: Why do fat people often develop serious and sometimes lifethreatening medical conditions?

The answer, it turns out, has little to do with the fat itself. It’s about each person’s ability to store it. With that understanding, scientists are now working on drug treatments to protect people from excess unstored fat and spare them from dire medical conditions.

The need is clear. One in three Americans and one in four adults worldwide have at least three conditions associated with obesity. Just one in 10 million people are estimated to suffer from the disorder that has affected Johnson, which can be caused by a rare gene mutation.

After coming to the United States as a college student, she saw a doctor for some bumps on her arms and was stunned to learn that they were cholesterol crystallising from her blood. Her cholesterol level was sky high.

Further exams revealed that she had other problems fat people can develop — a huge fatty liver, ovarian cysts, extraordinarily high levels of triglycerides.

Johnson’s doctor was baffled. The usual instructions to patients to lose weight made no sense in this case.

She ended up in the office of an endocrinologist, Maria New, who also was stumped but determined to find answers.

One day in 1996, New while giving a lecture at the National Institutes of Health posed her usual query: Did anyone know what might be wrong with her skinny patient?

Simeon Taylor, who was the chief of the diabetes branch at the National Institute of Diabetes and Digestive and Kidney Diseases, popped up from his chair. He had seen several patients like Johnson. They have lipodystrophy, he said, a rare genetic disorder that is characterised by an abnormal lack of fatty tissue.

Taylor was hoping to start a study with a new drug, a synthetic version of a hormone called leptin, that might help the patients. The study began in 2000 with Johnson as one of its first participants.

Leptin is released by fat cells and travels through the blood to the brain. The more fat on a person’s body, the more leptin is released. When fat levels are low, leptin levels in the brain are low, and the brain responds by increasing the person’s appetite, prompting the person to eat and gain weight. For someone like Johnson, who has almost no fat cells to signal the brain, the brain gets almost no leptin. To the brain, it seems as if she is starving. As a result, she receives continuous signals to eat. With leptin treatment, Johnson’s brain was tricked into responding as though she had abundant fat. Her insatiable hunger vanished. Fat disappeared from her liver, her blood glucose became normal, and so did her cholesterol and triglyceride levels.

Leptin treatment aided Johnson and brought her cholesterol and triglyceride levels back to normal