Abstract

Cancer-related and primary lymphedema (LE) are associated with the production of adipose tissue (AT). Nothing is known, however, about the lipid-based molecules that comprise LE AT. We therefore analyzed lipid molecules in lipoaspirates and serum obtained from LE patients, and compared them to lipoaspirates from cosmetic surgery patients and healthy control cohort serum. LE patient serum analysis demonstrated that triglycerides, HDL- and LDL-cholesterol and lipid transport molecules remained within the normal range, with no alterations in individual fatty acids. The lipidomic analysis also identified 275 lipid-based molecules, including triacylglycerides, diacylglycerides, fatty acids and phospholipids in AT oil and fat. Although the majority of lipid molecules were present in a similar abundance in LE and non-LE samples, there were several small changes: increased C20:5-containing triacylglycerides, reduced C10:0 caprinic and C24:1 nervonic acids. LE AT oil also contained a signature of increased cyclopropane-type fatty acids and inflammatory mediators arachidonic acid and ceramides. Interestingly C20:5 and C22:6 omega-3-type lipids are increased in LE AT, correlating with LE years. Hence, LE AT has a normal lipid profile containing a signature of inflammation and omega-3-lipids. It remains unclear, however, whether these differences reflect a small-scale global metabolic disturbance or effects within localised inflammatory foci.

Highlights

  • Lymphedema (LE) is a condition where lymphatic fluid accumulates within interstitial tissues causing swelling

  • This study examined lipoaspirates from patients with primary and cancer-related limb LE, comparing the tissue to that obtained from patients undergoing cosmetic liposuction surgery; it documents many similarities as well as specific small differences in lipidomic profiles between LE and non-LE adipose tissue (AT)

  • Cosmetic liposuction surgery usually involves the use of saline in the tissue extraction procedure, but no additional fluid is required for LE liposuction

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Summary

Introduction

Lymphedema (LE) is a condition where lymphatic fluid accumulates within interstitial tissues causing swelling. There is a surgical treatment option for people living with advanced AT rich LE: liposuction surgery [9,10,11,12] which physically removes the AT that predominates the affected area [7,8]. This treatment is highly beneficial for LE patients, immediately reducing the LE affected limb size, the reasons for the production of LE AT are still emerging and the LE pathology is incompletely understood [13]. To begin to better understand the pathobiology of AT production in advanced LE we examined the serum lipids and experimentally generated the first AT lipid profiles of advanced cancer-related LE patients and compared them with normal serum, and to anatomically-matched arm and leg normal, non-LE, AT

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