Adipose Tissue Biology and Effect of Weight Loss in Women With Lipedema

UNLABELLED: Lipedema is a lipodystrophic disease that is typically characterized by a marked increase in lower-body subcutaneous adipose tissue that is purported to have increased inflammation and fibrosis, have impaired microvascular/lymphatic circulation, and be resistant to reduction by weight loss therapy. However, these outcomes have not been adequately studied. We evaluated body composition, insulin sensitivity, metabolic health, and adipose tissue biology in women with obesity and lipedema (Obese-LIP) before and after moderate (∼9%) diet-induced weight loss. At baseline, people with Obese-LIP had ∼23% greater leg fat mass, ∼11% lower android-to-gynoid ratio, and ∼48% greater insulin sensitivity (all P < 0.05) than women matched on age, BMI, and whole-body adiposity. In Obese-LIP, macrophage content and expression of genes involved in inflammation and fibrosis were greater, whereas lymph/angiogenesis-related genes were lower in thigh than abdominal subcutaneous adipose tissue. Weight loss improved insulin sensitivity and decreased total fat mass, with similar relative reductions in abdominal and leg fat masses, but without changes in markers of inflammation and fibrosis. These results demonstrate that affected adipose tissue in women with lipedema is characterized by increased inflammation and fibrogenesis, and alterations in lymphatic and vascular biology. Moderate diet-induced weight loss improves metabolic function and decreases lower-body adipose tissue mass. ARTICLE HIGHLIGHTS: We sought to increase our understanding of the pathophysiology of lipedema and the effects of weight loss. We examined whether there are differences in upper- and lower-body adipose tissue biology in lipedema and whether adipose tissue is affected by weight loss. Women with obesity and lipedema have decreased expression of genes related to lymphatic/vascular function and increased expression of genes related to fibrosis and inflammation in thigh compared with abdominal subcutaneous adipose tissue; weight loss increased insulin sensitivity and decreased leg fat but did not affect adipose tissue inflammation or fibrosis. Weight loss should be the first-line therapy for women with obesity and lipedema.