Unraveling the Mystery: A Rare Fat Loss Disease and its Link to Diabetes
Many of us might have a negative view of fat tissue, but scientists now recognize adipose as a crucial and metabolically active organ, performing vital functions within the body. However, excessive fat can contribute to conditions like diabetes and heart disease in obesity.
Intriguingly, a rare genetic and autoimmune disorder known as familial partial lipodystrophy type 2 (FPLD2) presents a paradox. It involves the abnormal loss and distribution of adipose tissue, which can also lead to diabetes and metabolic disease. This has long puzzled Elif Oral, M.D., a clinician and Professor in the Division of Metabolism, Endocrinology, and Diabetes.
Oral's research career has been dedicated to understanding the underlying mechanism of pathological fat loss in patients with lipodystrophy syndromes. With the generous help of patients with FPLD2, she, along with her team, has finally found some answers.
The team, including Ormond MacDougald, Ph.D., Professor of Molecular & Integrative Physiology, and graduate student researcher Jessica Maung, Ph.D., created a mouse model to study the lamin A/C gene, which is mutated in patients with FPLD2. They observed that dramatic gene expression changes in adipocytes lead to impaired lipid handling and storage functions.
Additionally, the fat cells and immune cells within the adipose tissue became pro-inflammatory, and the mitochondria inside the fat cells became dysfunctional. These effects collectively create an unhealthy environment, leading to the disappearance of the tissue.
Without healthy adipose tissue, the normal maintenance of lipids and release of metabolic hormones are disrupted, resulting in metabolic diseases like diabetes and fatty liver disease. Oral emphasizes the importance of healthy fats in maintaining metabolism, stating that Type 2 diabetes is not just a disease of beta cells but also of fat cells.
The team's findings offer valuable insights for future therapeutic targets, aiming to prevent the disappearance of adipose tissue and correct metabolic dysfunction in this disease. MacDougald praises the collaboration between clinical researchers and basic science physiologists, highlighting the importance of patient involvement in developing therapies and understanding their disease.
The research, published in The Journal of Clinical Investigation, uncovers the intricate relationship between rare fat loss diseases and diabetes, opening new avenues for treatment and prevention.
