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

Abstract

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 aftermoderate (~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) thanwomenmatched 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 fatmass, with similar relative reductions in abdominal and leg fatmasses, 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 tissuemass. This study was supported by the Lipedema Foundation; National Institutes of Health grants DK56341 (Nutrition Obesity Research Center), DK20579 (Diabetes Research Center), DK052574 (Digestive Disease Research Center), and UL1TR002345 (Clinical and Translational Science Award); the Foundation for Barnes-Jewish Hospital; and a Saint Louis University Research Fund.