It is believed that adipose tissue is something that the body is better off without. However, scientists now know that adipose tissue is an active and essential organ that supports many important processes such as energy storage, hormone production, and metabolic regulation.
Too much fat can increase your risk of diabetes, heart disease, and other health problems. However, the opposite can be dangerous. In rare genetic and autoimmune diseases such as familial partial lipodystrophy type 2 (FPLD2), abnormal fat loss and uneven fat distribution can lead to diabetes and other metabolic diseases.
The longstanding mystery of fat loss
Dr. Elif Oral, a clinician and professor in the Department of Metabolism, Endocrinology, and Diabetes, has spent much of his career trying to understand this apparent contradiction. Her goal is to uncover why pathological fat loss damages metabolism and improve treatment options for people with lipodystrophy syndrome.
Working with patients with FPLD2, Oral joins Professor of Molecular and Integrative Physiology Ormond McDougald, Ph.D., graduate student researcher Jessica Maun, Ph.D., and a broader collaborative team to investigate what is happening inside diseased adipose tissue.
“The simple explanation is that something really catastrophic is happening inside every adipocyte (adipocyte),” Maun says.
To study this process, researchers developed a mouse model in which they could specifically switch off the lamin A/C gene in adipocytes. This is the same gene that is mutated in FPLD2 patients.
fat cells lose their normal function
The researchers tested both animal models and tissue donated by patients. They discovered major changes in gene activity that prevent fat cells from properly processing and storing lipids.
At the same time, adipocytes and immune cells within the adipose tissue transitioned into a pro-inflammatory state. Mitochondria within fat cells also stop functioning properly. Mitochondria help cells produce energy, so mitochondrial disorders can have far-reaching effects on cellular health.
Dr. Maun said, “All these effects combine to create the perfect environment for tissue to become really unhealthy and eventually die.”
Why healthy fats protect your metabolism
When healthy adipose tissue is lost, the body is unable to manage lipids and release metabolic hormones in the normal way. This breakdown can lead to serious conditions such as diabetes and fatty liver disease.
“This really highlights the importance of healthy fats in keeping your metabolism intact and functional,” Oral said. “People think of type 2 diabetes as a disease of the beta cells, but it’s actually a disease of the fat cells as well.”
Beta cells are insulin-producing cells in the pancreas. Adipocytes play a central role in diabetes, but new discoveries show that they are also deeply involved in maintaining normal blood sugar control and metabolic health.
New targets for future treatments
Researchers hope their findings will point to new therapeutic targets. One possibility is to protect adipose tissue before it deteriorates, preventing fat cell loss and reducing metabolic damage caused by disease.
This study also highlights the importance of close collaboration between laboratory scientists, clinicians, and patients.
“I think this study is an excellent example of collaboration between translational clinical researchers and basic science physiologists,” McDougald said. “We also cannot overstate the importance of our patient populations, their involvement in treatment development, and their dedication to understanding their disease.”
Other authors include Rebecca L. Schill, Akira Nishii, Maria Foss de Freitas, Bonje N. Obua, Marcus Nygård, Maria D. Mendez-Casillas, Isabel DK Hermsmeyer, Donatella Gilio, Ozge Besci, Yang Chen, Brian Desrosiers, Rose E. Adler, Anabela D. Golik, Hive Guler, Ceyukimes Contains. Mori, Romina M. Uranga, Jill Lee, Hadra Hariri, Liping Zhang, Anderson de Paula Souza, Keegan S. Horse, Kenneth T. Lewis, Taryn A. Hetrick, Paul Cederna, Carrie N. Lumen, and Suzanne Mandrup.
