Cifarelli Vincenza, Smith Gordon I, Gonzalez-Nieves Silvia, Samovski Dmitri, Palacios Hector H, Yoshino Jun, Stein Richard I, Fuchs Anja, Wright Thomas F, Klein Samuel
Department of Pharmacology and Physiology, Saint Louis University School of Medicine, St. Louis, MO.
Center for Human Nutrition, Washington University School of Medicine, St. Louis, MO.
Diabetes. 2025 Mar 1;74(3):308-319. doi: 10.2337/db24-0890.
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.
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.
脂肪性水肿是一种脂肪营养不良性疾病，其典型特征是下半身皮下脂肪组织显著增加，据称存在炎症和纤维化加剧、微血管/淋巴循环受损以及对减肥治疗有抵抗性。然而，这些结果尚未得到充分研究。我们评估了肥胖合并脂肪性水肿（肥胖 - 脂肪性水肿，Obese - LIP）女性在适度（约9%）饮食诱导体重减轻前后的身体成分、胰岛素敏感性、代谢健康和脂肪组织生物学特性。在基线时，与年龄、体重指数（BMI）和全身肥胖程度匹配的女性相比，Obese - LIP患者的腿部脂肪量多约23%，腰臀比低约11%，胰岛素敏感性高约48%（所有P < 0.05）。在Obese - LIP患者中，与腹部皮下脂肪组织相比，大腿巨噬细胞含量以及参与炎症和纤维化的基因表达更高，而与淋巴/血管生成相关的基因更低。体重减轻改善了胰岛素敏感性并降低了总脂肪量，腹部和腿部脂肪量的相对减少相似，但炎症和纤维化标志物没有变化。这些结果表明，脂肪性水肿女性受影响的脂肪组织具有炎症和纤维生成增加以及淋巴和血管生物学改变的特征。适度饮食诱导的体重减轻改善了代谢功能并减少了下半身脂肪组织量。
我们试图增进对脂肪性水肿病理生理学以及体重减轻影响的理解。我们研究了脂肪性水肿患者上下半身脂肪组织生物学是否存在差异以及脂肪组织是否受体重减轻影响。与腹部皮下脂肪组织相比，肥胖合并脂肪性水肿的女性大腿中与淋巴/血管功能相关的基因表达降低，与纤维化和炎症相关的基因表达增加；体重减轻增加了胰岛素敏感性并减少了腿部脂肪，但未影响脂肪组织炎症或纤维化。体重减轻应是肥胖合并脂肪性水肿女性的一线治疗方法。
