Altered mitochondrial function is a hallmark of lipedema adipocytes
Faculty Mentor Name
Dr. Atefeh Rabiee
Research or Creativity Area
Pharmacy
Abstract
Adipose tissue is a heterogenous organ acting as a master regulator of overall metabolic state. Adipose tissue consists of highly specialized adipocytes that regulate energy storage, endocrine signaling, and thermogenesis. Based on function, adipocytes can be white, beige or brown; aptly named because of their appearance. White adipocytes, most well-known traditionally act as an energy reservoir and store fat. Brown adipocytes on the other hand; due to their high mitochondrial density and in turn high iron content (which gives them their appearance) can burn calories and release energy in the form of heat. However, brown adipocytes are only present in a small amount in the neck and shoulder regions of human adults, making it a difficult target to approach. Beige adipocytes are an inducible type of white fat that remodels into thermogenic brown-like/beige adipose tissue upon exposure to external stimuli such as cold temperature, chronic exercise, and certain diets. Thus, it is an especially attractive target for treating fat disorders like obesity due to its abundance in subcutaneous fat depot in the leg and hip region.
Lipedema is a chronic, progressive adipofascial disorder affecting predominantly females, characterized by bilateral symmetrical deposition of subcutaneous adipose tissue primarily in the lower limbs, gluteal region, and hips. Unlike generalized obesity, lipedema-associated adipose tissue exhibits pronounced resistance to conventional weight reduction strategies, including caloric restriction, physical activity, bariatric procedures, and pharmacologic anti-obesity therapies. The pathophysiology of lipedema remains poorly understood, though mitochondrial dysfunction is increasingly implicated in its resistance to weight loss. Our study investigates the role of mitochondria the primary organelles governing cellular metabolism within adipocytes, to understand their impact on lipedema pathophysiology. Adipose-derived stem cells (ADSCs) from subcutaneous adipose tissue were obtained from lipedema, lean, and obese donors. These were then differentiated into mature adipocytes and given a thermogenic stimulus (forskolin). Proteomic analysis revealed a distinct subset of mitochondrial proteins—involved in β-oxidation and the TCA cycle that are differentially regulated in lipedema adipocytes. Our results to date provide evidence that mitochondrial function may play a crucial role in the persistent fat accumulation characteristic of lipedema.
Altered mitochondrial function is a hallmark of lipedema adipocytes
Adipose tissue is a heterogenous organ acting as a master regulator of overall metabolic state. Adipose tissue consists of highly specialized adipocytes that regulate energy storage, endocrine signaling, and thermogenesis. Based on function, adipocytes can be white, beige or brown; aptly named because of their appearance. White adipocytes, most well-known traditionally act as an energy reservoir and store fat. Brown adipocytes on the other hand; due to their high mitochondrial density and in turn high iron content (which gives them their appearance) can burn calories and release energy in the form of heat. However, brown adipocytes are only present in a small amount in the neck and shoulder regions of human adults, making it a difficult target to approach. Beige adipocytes are an inducible type of white fat that remodels into thermogenic brown-like/beige adipose tissue upon exposure to external stimuli such as cold temperature, chronic exercise, and certain diets. Thus, it is an especially attractive target for treating fat disorders like obesity due to its abundance in subcutaneous fat depot in the leg and hip region.
Lipedema is a chronic, progressive adipofascial disorder affecting predominantly females, characterized by bilateral symmetrical deposition of subcutaneous adipose tissue primarily in the lower limbs, gluteal region, and hips. Unlike generalized obesity, lipedema-associated adipose tissue exhibits pronounced resistance to conventional weight reduction strategies, including caloric restriction, physical activity, bariatric procedures, and pharmacologic anti-obesity therapies. The pathophysiology of lipedema remains poorly understood, though mitochondrial dysfunction is increasingly implicated in its resistance to weight loss. Our study investigates the role of mitochondria the primary organelles governing cellular metabolism within adipocytes, to understand their impact on lipedema pathophysiology. Adipose-derived stem cells (ADSCs) from subcutaneous adipose tissue were obtained from lipedema, lean, and obese donors. These were then differentiated into mature adipocytes and given a thermogenic stimulus (forskolin). Proteomic analysis revealed a distinct subset of mitochondrial proteins—involved in β-oxidation and the TCA cycle that are differentially regulated in lipedema adipocytes. Our results to date provide evidence that mitochondrial function may play a crucial role in the persistent fat accumulation characteristic of lipedema.
