Lipodystrophy and leptin harmone treatment
for A small group of thin patients who develop disorders typically tied to
obesity and Diabetes 2
A small group of thin patients who develop disorders typically tied to
obesity pose a medical mystery and a potential opportunity for scientists.As in the case of Claire Walker Johnson of Queens, 55, of Queens, developed Type 2 diabetes and a fatty liver, among other problems related to obesity, despite weighing only 119 pounds.
Ms. Johnson, had no idea anything was amiss. She was very thin and always ravenous, but in Jamaica, where she was born, many children were skinny, , and no one thought much of it. She seemed healthy, and she developed normally through adolescence.
She was a medical mystery. No matter how much she ate, she never gained weight.And yet, she had the conditions many obese people develop — Type 2 diabetes, high blood pressure, high cholesterol and, most strikingly, a liver buried in fat. The answer has little to do with the fat itself. It’s about each person’s ability to store it.
Oone in four adults worldwide have at least three conditions associated with obesity such as diabetes, highcholesterol and high blood pressure — a combination of disorders that doubles their risk of heart attacks and strokes. In addition, a grave accumulation of fat in their livers caused by obesity that can lead to liver failure.a disorder that can be caused by a gene mutation so rare it is estimated to affect just one in 10 million people, including, Ms. Johnson.
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 crystallizing 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.
Ms. Johnson’s doctor was baffled. The usual instructions to patients to lose weight made no sense in this case. “He said, ‘I don’t think I can help you,’” she recalled.
She ended up in the office of an endocrinologist, Dr. Maria New, who also was stumped but determined to find answers. She measured Ms. Johnson: 5 feet 7 inches. She weighed her: 119 pounds.
Dr. New spent years asking specialists at every medical conference she attended about Ms. Johnson. One day in 1996, she was giving a lecture at the National Institutes of Health and posed her usual query: Did anyone know what might be wrong with her skinny patient?
Dr. 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 Ms. Johnson. They have lipodystrophy, he said, a rare genetic disorder that is characterized by an abnormal lack of fatty tisues
Dr. Taylor told Dr. New. During his study on insulin resistance, the cause of Type 2 diabetes, had found that people with lipodystrophy had the most severe insulin resistance he had ever seen, and they were far from obese.
He had found that hormone called leptin, that might help the patients.
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 Ms. 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, Ms. 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. Thus Dr. Maria New, an endocrinologist, helped Ms. Johnson figure out what was causing her symptoms.
Now researchers have moved on to the next phase of the investigation, trying to identify the poison in fat that is causing all these problems and find a way to block it. At least two chemicals seem to be involved.produced from fatty acids — made from the food a person eats —.diacylglycerol,
One sure way to get rid of it in liver and muscle cells is to lose weight — to stop providing the body with more calories than its fat tissue can handle
another class of compounds, called ceramides. they are produced from fat floating in the blood and are unable to get into fat tissue for storage or degradation. They, too, cause insulin resistance. and can also kill cells if their levels become high and can bring on inflammatory responses. And inflammation, is a hallmark of obesity.