UTSW Researchers Find Autoantibody Linked to Rare Disorder That Destroys Fat

The UT Southwestern researchers discovered the first molecular biomarker for AGL, a rare disorder in which fat deposits are destroyed, causing patients to have dangerously low body fat, signs of accelerated aging, and severe metabolic diseases including diabetes and fatty liver.

Researchers at UT Southwestern Medical Center in Dallas have made a discovery that could help diagnose and unlock new therapies for people with acquired generalized lipodystrophy (AGL).

The researchers discovered the first molecular biomarker for AGL, a rare disorder in which fat deposits are destroyed, causing patients to have dangerously low body fat, signs of accelerated aging, and severe metabolic diseases including diabetes and fatty liver.

Discovery ‘provides a new diagnostic tool’

“The discovery of this autoantibody provides a new diagnostic tool for AGL patients and could potentially result in novel therapeutic options,” Abhimanyu Garg, M.D., professor of internal medicine, section chief of Nutrition and Metabolic Diseases in the Division of Endocrinology, and director of Metabolic Diseases in UT Southwestern’s Center for Human Nutrition, said in a statement.

Garg was one of three senior authors of the study, published in Diabetes, conducted in collaboration with colleagues at the University of California, San Francisco, and institutions in France, Norway, and Russia.

Underlying cause remains unclear

According to UTSW, the underlying cause of AGL, which is most often diagnosed in children but also can appear in adults, has so far remained unclear. Roughly 100 cases have been reported worldwide, making it difficult to study the commonalities among patients.

For years, researchers have suspected the disorder is an autoimmune condition, in which a person’s immune system attacks the body, UTSW said. Researcher, however, had been unable to pinpoint any unusual or unique autoantibodies in AGL patients, the medical center said.

In their research, Garg and his colleagues utilized their UT Southwestern biorepository containing blood, DNA, and clinical data collected from 46 patients with AGL over the past 30 years.

World’s largest collection of data on AGL patients

“We now have the largest collection of data on AGL patients in the world,” Garg said. “The banked samples from these patients were key to our new discovery.”

UTSW said the team sought to find antibodies against nearly 19,500 different human proteins in the blood samples from the patients and healthy controls, homing in on the perilipin-1 autoantibody as the key finding differentiating people with AGL from those without the disease.

Perilipin-1 is a protein known to play a role in the storage of fat molecules in fat cells, UTSW said. The autoantibody was found to be present in 17 of the 46 patients but in none of the controls.

That led the team to conclude that the perilipin-1 autoantibody – which would direct the immune system to attack the protein and therefore harm fat cells – might play a role in the disease.

UTSW said that additional detailed profiling of the patients whose blood contained the perilipin-1 autoantibody showed that those with one subtype of AGL, known as AGL with panniculitis, were even more likely to have them.

Panniculitis is a process whereby immune cells infiltrate fat tissue, causing destruction and death of fat cells. The team also discovered that laboratory mice known to develop AGL-like disease also had the autoantibody to perilipin-1.

Further work is needed

Researchers said that they need to do further work to understand the prevalence of the perilipin-1 autoantibody among patients with AGL and related disorders, as well as whether an immunotherapy drug or procedure could remove or block the autoantibody to treat those developing AGL.

Other UTSW researchers who contributed to the study include Anil K. Agarwal, Xilong Li, and Chengsong Zhu, UTSW said.

The research was supported by funding from the National Institutes of Health and the Southwestern Medical Foundation.

Get on the list.
Dallas Innovates, every day.

Sign up to keep your eye on what’s new and next in Dallas-Fort Worth, every day.

One quick signup, and you’re done.
View previous emails.

R E A D   N E X T

  • The Ho Din Award honors those who exemplify the unique combination of medical wisdom and human understanding that distinguishes all great physicians.Leading with a heart of service, Cayenne L. Price, M.D., hopes to create as much of an impact in her community as possible while caring for her patients.

  • As many North Texans try to move on from the pandemic, Dr. Bell is focused on the "tens of millions of patients" who've developed long-haul COVID—and who are experiencing life-altering symptoms long after their COVID-19 infection cleared.

  • The Perot family’s support will expand the number of students admitted to UT Southwestern's dual-degree program as well as research disciplines in which they study, to include biomedical engineering, computational biology, bioinformatics, and data science. The funding will enhance the curriculum and experiences of Medical Scientist Training Program students and increase efforts to recruit students from elite U.S. colleges, including top international students who want to stay in the U.S. for their careers.

  • Over 150 scientists across dozens of departments will be part of the elite National Institutes of Health-funded, university-wide interdisciplinary research center. Dallas' UT Southwestern Medical Center is the only institution in Texas to be selected for the NIH initiative. UTSW wants to translate scientific discoveries into new therapeutic strategies for the prevention and treatment of obesity, which it describes as a chronic disease affecting more than 40% of the U.S. population, with medical costs nearing $175 billion.

  • As one of the nation’s premier academic medical centers, nurturing employees for management and leadership roles is mission critical. The medical center, with its workforce of nearly 23,000, received the 2022 BOLD award for its leadership development. “As we do with our scientific, medical, and training missions, we apply data-driven strategies to nurture leaders who contribute to our institution’s culture of integrity, inclusiveness, and collaboration, and extend those qualities throughout the organization,” Holly Crawford said.