Understanding the Importance of Healthy Fats

For years, fat tissue has been viewed as an unwanted presence in the body, with many people aiming to eliminate it to reduce the risk of chronic diseases such as diabetes and heart disease. However, a new study reveals that fat tissue plays a crucial role in maintaining our overall health, and losing the wrong type of fat can actually trigger diabetes.

Scientists have long known that too much fat can increase the risk of various health problems, including diabetes, heart disease, and other metabolic diseases. However, research has also shown that the opposite can be just as detrimental. In rare genetic and autoimmune conditions such as familial partial lipodystrophy type 2 (FPLD2), abnormal fat loss and uneven fat distribution can lead to diabetes and other metabolic diseases.

Elif Oral, M.D., a clinician and Professor in the Division of Metabolism, Endocrinology and Diabetes, has dedicated her career to understanding the apparent contradiction between fat loss and diabetes. Her goal has been to uncover why pathological fat loss damages metabolism and to improve treatment options for people with lipodystrophy syndromes.

Working with patients who have FPLD2, Oral joined Ormond MacDougald, Ph.D., Professor of Molecular & Integrative Physiology, graduate student researcher Jessica Maung, Ph.D., and a broader collaborative team to investigate what happens inside diseased fat tissue. The researchers developed a mouse model in which they could switch off the lamin A/C gene specifically in adipocytes, the same gene that is mutated in people with FPLD2.

The researchers examined both the animal models and tissue donated by patients and found major changes in gene activity that prevented fat cells from properly processing and storing lipids. At the same time, the adipocytes and the immune cells within the fat tissue shifted into a pro-inflammatory state, and the mitochondria inside the fat cells stopped functioning normally.

The researchers’ findings suggest that when healthy adipose tissue is lost, the body can no longer manage lipids or release metabolic hormones in the usual way, leading to serious conditions such as diabetes and fatty liver disease. This is a significant discovery, as it highlights the importance of healthy fats in keeping metabolism intact and functional.

The researchers hope their findings will point to new therapeutic targets, such as protecting adipose tissue before it deteriorates, preventing fat cells from disappearing, and reducing the metabolic damage caused by the disease. The work also emphasizes the importance of close collaboration between laboratory scientists, clinicians, and patients.