Biomarker for lipedema, other lymphatic diseases discovered
Researchers have identified a molecule that ties lipedema to other lymphatic diseases, such as lymphedema, and distinguishes it from obesity.
Throughout her life, Kristy has been told she was obese and needed to lose weight. She was teased and tormented for looking fat. Doctors didn’t believe her when she said she was constantly dieting but still couldn’t lose weight. She assumed that the unsightly fat on her hips and lower body, which often caused her pain, was her own fault.
When she finally discovered, just a year ago at the age of 53, that she had a little known and poorly understood disease called lipedema, which made it almost impossible to lose a good portion of her weight, she burst into tears of relief.
“I started sobbing,” said Kristy, who asked that her real name not be used. “Now I know the fat caused by lipedema is as difficult to get rid of as it is for a camel to lose its hump. You have to be close to starving to death to get rid of it.”
Lipedema is part of a family of medical problems called fat disorders and is often confused with obesity, said Stanley Rockson, MD, professor of cardiovascular medicine and the Allan and Tia Neill Professor of Lymphatic Research and Medicine at the Stanford School of Medicine. It causes fatty tissue to collect in the lower portion of the body, primarily the hips, but can affect the arms as well. It is often triggered by hormonal changes in women, particularly after life events such as puberty or pregnancy, or during menopause, but it also has a potential genetic component. Until recently, little was known about its scientific underpinnings.
Now, for the first time, Rockson and his colleagues have uncovered a biomarker — in this case, a particular molecule that can be detected in patients — that confirms that lipedema is related to other lymphatic diseases, such as lymphedema, distinguishing it from obesity.
The findings were published June 11 in JCI Insights. Rockson shares senior authorship with Guillermo Oliver, PhD, director of the Center for Vascular and Developmental Biology at Northwestern University. The lead author is Wanshu Ma, PhD, a research scientist at Northwestern University.
“I immediately contacted thousands of women when I heard about this study and told them it’s a game changer,” said Catherine Seo, PhD, a patient advocate and founder and executive director of the Lipedema Project. She is the co-author of the book Lipedema: The Disease They Call Fat: An Overview for Clinicians. “Now with this biomarker, there is hope for a blood test to identify lipedema. That is major. Absolutely major.”
Often confused with obesity
Lipedema is often confused with obesity because that’s what it looks like, and few doctors are trained to know the difference, Rockson said.
“Many of these patients struggle with simple validation that they have a pathological entity,” said Rockson, who has been treating patients with the disorder and studying the lymphatic system for almost three decades. “This is a disease — it’s not their fault — yet they are often denied medical care and denied insurance coverage.”
Rockson first began treating patients with unexplained edema, or swelling, in the limbs in the early 1990s. As his hunt for treatments progressed, it led him on a lifelong journey to understand the lymphatic system. He has long suspected that disorders like lymphedema and lipedema are caused by defects in the lymphatic system, but there has been little research to support that view.
“My hypothesis is that a lymphatic defect damages the ability of subcutaneous fat to clear fluids from its tissues,” Rockson said. “It becomes swollen and inflamed and experiences this abnormal growth. These cells, which are designed to store fat, get to a stage where they are able to store it but unable to release it. No amount of caloric restriction will make them smaller.”
Lipedema is often confused with lymphedema, a similar disease that also causes swelling in the limbs. But under the microscope, the two disorders look different, and the causes, while similar, involve different effects on the vasculature. Both are often confused with obesity.
‘A protein fingerprint’
“We wanted to see if we could find a biological marker for lymphedema and lipedema, and discriminate between those and obesity,” Rockson said. Working first in a mouse model for obesity developed by Oliver, who researches the lymphatic system, they found that platelet factor, a small protein, 4 is a biomarker for lymphatic-promoted disorders.
“We found a protein fingerprint that seemed to be uniquely associated with the mice that had a lymphatic defect but was not present in normal mice or the obese mice,” Rockson said. Analyzing human cells from 50 participants — 12 who were healthy, 37 with lymphedema, 11 with lymphovascular disease and 15 with lipedema — they found a similar fingerprint.
“What we found when we did the protein analyses was that Pf4 was uniquely elevated in all three categories of patients with lymphatic disease,” Rockson said. “It very clearly established that lipedema has the same biomarker.” This biomarker could also be useful in investigations into a variety of other diseases in which researchers have begun to suspect lymphatic dysfunction plays a role, such as Alzheimer’s disease, heart failure, glaucoma and diabetes.
The discovery of this biomarker also now creates potential for a blood test to diagnose lymphatic diseases in outpatient settings, Rockson said. Current methods of diagnosing both lymphedema and lipedema involve invasive and expensive imaging procedures and aren’t often used. A simple blood test could be a game changer, he said.
“Lipedema patients feel totally abandoned, and rightfully so,” Rockson said. “They have a disease that turns life upside-down and are told there is nothing wrong with them. To dignify it with proper identification is very important to people.”
Seo, who communicates with thousands of women around the world with lipedema, said that this new discovery has already changed how they view their disease.
“We know the degree and level of bias against fat,” she said. “I’ve heard it thousands of times from women like me. ‘My doctor says I’m fat, that I need to lose weight, that it’s my fault.’ If there’s pain, it’s ascribed to emotional or psychological issues. To confirm that it’s actually a disease is a breakthrough.”
Kristy said that she knows firsthand how painful it can be to live a life filled with this prejudice against fat. Dealing with insults has been a way of life for her.
“I used to hear stuff all the time, ‘It’s your fault. It’s just a matter of being good with God. If you’re good with God, there’s no way you’ll be overweight.’ This is the kind of crap I’ve gotten my entire life. What Dr. Rockson has done has meant so much to me.”
Researchers from Cornell University and the Spanish National Research Center contributed to this study. The research was supported by the National Institutes of Health (grants R01HL073402 and T32 HL134633) and the National Fund for Scientific and Technological Development of Chile.
Additional support came from the European Union Horizon.
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