Dilated Blood and Lymphatic Microvessels, Angiogenesis, Increased Macrophages, and Adipocyte Hypertrophy in Lipedema Thigh Skin and Fat Tissue

Abstract

Background and Aim. Lipedema is a common painful SAT disorder characterized by enlargement of fat primarily in the legs of women. Case reports of lipedema tissue samples demonstrate fluid and fibrosis in the interstitial matrix, increased macrophages, and adipocyte hypertrophy. The aims of this project are to investigate blood vasculature, immune cells, and structure of lipedema tissue in a cohort of women. Methods. Forty-nine participants, 19 controls and 30 with lipedema, were divided into groups based on body mass index (BMI): Non-Obese (BMI 20 to <30 kg/m2) and Obese (BMI 30 to <40 kg/m2). Histological sections from thigh skin and fat were stained with H&E. Adipocyte area and blood vessel size and number were quantified using ImageJ software. Markers for macrophages (CD68), mast cells (CD117), T cells (CD3), endothelial cells (CD31), blood (SMA), and lymphatic (D2-40 and Lyve-1) vessels were investigated by IHC and IF. Results. Non-Obese Lipedema adipocyte area was larger than Non-Obese Controls (p=0.005) and similar to Obese Lipedema and Obese Controls. Macrophage numbers were significantly increased in Non-Obese (p<0.005) and Obese (p<0.05) Lipedema skin and fat compared to Control groups. No differences in T lymphocytes or mast cells were observed when comparing Lipedema to Control in both groups. SMA staining revealed increased dermal vessels in Non-Obese Lipedema patients (p<0.001) compared to Non-Obese Controls. Lyve-1 and D2-40 staining showed a significant increase in lymphatic vessel area but not in number or perimeter in Obese Lipedema participants (p<0.05) compared to Controls (Obese and Non-Obese). Areas of angiogenesis were found in the fat in 30% of lipedema participants but not controls. Conclusion. Hypertrophic adipocytes, increased numbers of macrophages and blood vessels, and dilation of capillaries in thigh tissue of non-obese women with lipedema suggest inflammation, and angiogenesis occurs independent of obesity and demonstrates a role of altered vasculature in the manifestation of the disease.

Lipedema: A Call to Action!

“…Additionally, they described enhanced proliferation capacity of adipose‐derived stem, progenitor, and stromal cells, likely promoting adipogenesis. Interestingly, a recent study by Al‐Ghadban et al found that patients with lipedema and without concomitant obesity displayed hypertrophic adipocytes, increased numbers of macrophages and blood vessels, and dilation of capillaries in thigh fat compared with healthy controls. Such findings suggest that inflammation and angiogenesis may occur independently of obesity in lipedema and support the role of an altered microcirculation in the manifestation of the disease.…”

SVF-derived extracellular vesicles carry characteristic miRNAs in lipedema

“…This excess fluid in the interstitium potentially leads to growth of adipose tissue and hypoxia, which in turn might enhance angiogenesis of pathologic vessels 4,5 . The area of lymphatic vessels and the number of blood vessels were found increased in non-obese lipedema patients compared to controls 6 . Examination of adipose tissue from lipedema patients demonstrated hypertrophic adipocytes, crown-like structures and increased number of macrophages [6][7][8] .…”

Lipedema: A Painful Adipose Tissue Disorder

“…Men with lipedema have elevated estrogen level and low to absent testosterone levels resulting in cirrhosis, gynecomastia and hypogonadism [11][12][13]. While the exact etiopathogenesis of this disease is unknown [10,14], many studies have demonstrated that inflammatory cells, hypertrophic adipocytes, abnormal blood vessels and lymphatic dysfunction are associated with tissue damage and development of a fibrotic disease [14][15][16][17].…”

“…Dysfunction of lymphatic vessels results in accumulation of interstitial fluid (edema) in adipose tissues triggering inflammation by the recruitment of macrophages resulting in fibrosis and difficulty with weight loss. As a consequence, adipose tissue loses its elasticity suggesting that lipedema might be a connective tissue disorder [15,49]. Studies have also indicated that edema might induce growth of lipedema fat as well as hypoxia resulting in adipocyte cell death [50].…”

“…Studies have also indicated that edema might induce growth of lipedema fat as well as hypoxia resulting in adipocyte cell death [50]. DOI: http://dx.doi.org /10.5772/intechopen.88632 Further, morphologic changes in lymphatic vessels and accumulation of interstitial fluid are present in some women with lipedema, with no change in transport of lymphatic fluid, which suggests these individuals might have a higher risk of progressing to lipo-lymphedema especially in advanced stages of lipedema [15,51]. Accurate diagnosis of lipedema in association with lymphedema is essential for treating and following up of lipedema patients.…”