Adipocytes are larger in lymphedematous extremities than in controls

Abstract

Lymphedema is caused by dysfunctional lymph vessels or as a complication of cancer treatment leading to edema and adipose tissue deposition. One hypothesis is that adipocyte hypertrophy contributes to the volume increase in lymphedema. The aim of the study was to compare adipocyte size in arm and leg lymphedema and controls. The adipocyte size difference was also compared between the arms and legs. Furthermore, any link between adipocyte size difference and gender, lymphedema onset, duration, previous radio-and chemotherapy was studied, as well as any relationship to total excess volume increase in the extremities, body mass index (BMI) and body weight. Adipose tissue biopsies from the lymphedematous and non-affected extremities were taken from 47 patients. The adipocytes sizes were measured using an Olympus PROVIS microscope, Olympus DP50 camera (Olympus, Tokyo, Japan) and ImageJ program (NIH, Bethesda, MD). Additional information was obtained from the Lymphedema Center database. The data were assembled in Excel and statistics was calculated in SPSS V R Statistics 23 (IBM V R , Armonk, NY). The adipocyte size (mean ± SEM) in the lymphedematous extremities was significantly larger, 8880 ± 291 lm 2 , compared to the adipocyte size in the non-affected extremities, where it was 7143 ± 280 lm 2 , i.e. 24% larger (p < .001). The adipocyte size increase was larger in arm than in leg lymphedema. No correlation was found between adipocyte size and gender or onset. However, a negative correlation was found between adipocyte size difference and duration. No correlation was found between adipocyte size and previous chemo-or radiotherapy. There was a positive correlation between adipocyte size and BMI. Hypertrophy of adipocytes was seen in the lymphedematous extremities versus control and contributes to the excess volume.

Is Lymphedema a Systemic Disease? A Paired Molecular and Histological Analysis of the Affected and Unaffected Tissue in Lymphedema Patients

“…It is well established that an increased deposition and remodeling of adipose tissue characterized by hypertrophy occurs in the early years of lymphedema onset [ 18 ]. These clinical observations, as reported by Zhang et al [ 19 ], have been further confirmed in lymphedema experimental models—defined as increased lipid content and the expression of adipogenesis-related genes [ 20 , 21 ].…”

“…A number of well-known histological hallmarks were identified in the lymphedematous tissue. First of all, increased epidermal thickness was identified in the edematous tissue [ 17 , 19 , 26 ], which is used as a primary outcome measure for the efficacy of lymphedema treatments, such as the anti-inflammatory drug ketoprofen or anti-Th2 immunotherapy [ 10 , 27 ]. Fibrosis, a well-known hallmark and key driver of lymphedema, was significantly increased in the lymphedematous adipose tissue, but to our surprise, increased collagen deposition was noted in the non-lymphedematous tissue as well.…”

The Impacts of Lymph on the Adipogenesis of Adipose-Derived Stem Cells

“…Zhang et al also reported that the size of adipocytes from lymphedema extremities was greater than that from normal extremities. 33 The increase of oil red O amount was attributable to the increase in the size of adipocytes, not the number of adipocytes by proliferation from ASCs. ASCs with lymph culture resulted in increased cell differentiation rather than cell proliferation.…”

The impact of obesity on chronic oedema/lymphoedema of the leg – An international multicenter cross-sectional study (LIMPRINT)

“…T-cell inhibition/depletion of CD4+ cells decrease the severity of lymphoedema in obese animals [9,34,35]. The human lymphoedema fat tissue appear different compared to normal adipose tissue, with 24% larger [36] and highly variable adipocytes in size [10] compared to adipose tissue. Larger lobules, more collagen and a decreased number of M2 macrophages is also seen in lymphoedema adipose tissue [10].…”