Adipose tissue biology and effect of weight loss in women with lipedema

Lipedema is a lipodystrophic disease characterized by marked increases in lower-body subcutaneous adipose tissue, anecdotally reported to: i) increase inflammation and fibrosis and impair microvascular and lymphatic circulation in the affected adipose tissue, ii) reduce risk of developing obesity-related cardiometabolic abnormalities; and iii) be resistant to diet-induced weight loss. To further our understanding of lipedema, we examined body composition, metabolic health and adipose tissue bology in women with obesity and lipedema (Obese-LIP) at baseline and following ~9% diet-induced weight loss. At baseline, people with Obese-LIP had ~23% greater leg fat mass, ~11% lower android-to-gynoid ratio and ~54% greater insulin sensitivity compared to women matched on age, body mass index and whole-body fat mass. In the Obese-LIP group, total and proinflammatory macrophage content and expression of inflammation and fibrosis-related genes were greater while lymph/angiogenesis-related genes were lower in subcutaneous femoral compared to abdominal adipose tissue. Diet-induced weight loss improved insulin sensitivity and decreased total fat mass due to similar reductions in abdominal and leg fat masses, with minimal effect on markers of adipose tissue inflammation/fibrosis and lymph/angiogenesis. Our study provides important insights into the pathophysiology of lipedema and suggests diet-induced weight loss should be the cornerstone therapy in people with Obese-LIP.