Lipedema Research-Quo Vadis?

Abstract

When studying the current literature, one might get the impression that lipedema is a "modern" disease, with increasing incidence and augmenting prevalence throughout Western countries during the last decade. However, a quick look into older textbooks shows that disproportionate accumulation of fat in female bodies has long been known without being recognized as an independent disease. Nevertheless, it was not until 1940 that Allen and Hines described a "syndrome characterized by fat legs and orthostatic edema" in a seminal publication. The mere awareness that people who have lipedema are not just overweight but suffer from a yet poorly defined pathological condition, may be considered a decisive leap forward in the understanding of lipedema. A number of comprehensive publications have since dealt with the clinical presentation of lipedema and have provided the first clues towards the potential pathological mechanisms underlying its initiation and progression. Nevertheless, despite all effort that has been undertaken to unravel lipedema pathology, many questions have remained unanswered. What can be deduced with certainty from all experimental and medical evidence available so far is that lipedema is neither a cosmetic problem nor is it a problem of lifestyle but should be accepted as a serious disease with yet undetermined genetic background, which makes women's lives unbearable from both a physical and psychological point of view. To date, results from clinical inspections have led to the categorization of various types and stages of lipedema, describing how the extremities are affected and evaluating its progression, as demonstrated by skin alterations, adipose tissue volume increase and physical and everyday-behavioral impediments. There is accumulating evidence showing that advanced stages of lipedema are usually accompanied by excessive weight or obesity. Thus, it is not unreasonable to assume that the progression of lipedema is largely driven by weight gain and the pathological alterations associated with it. Similarly, secondary lymphedema is frequently found in lipedema patients at advanced stages. Needless to say, both conditions considerably blur the clinical presentation of lipedema, making diagnosis difficult and scientific research challenging. The present literature review will focus on lipedema research, based on evidence fromex vivo and in vitro data, which has accumulated throughout the last few decades. We will also open the discussion as to whether the currently used categorization of lipedema stages is still sufficient and up-to-date for the accurate description of this enigmatic disease, whose name, strangely enough, does not match its pathologic correlate.

Keywords: adipose tissue; in vitro and ex vivo studies; lipedema.

Figure 1

Biological processes suggested to be affected in lipedema pathology, as evidenced by data from ex vivo and in vitro research.

Figure 2

(a–c): In vitro differentiated adipocytes show multilocular lipid droplets after 21 days of adipogenic stimulation from (a) light microscopy (live cell imaging) (scale bar: 100 µm); (b) scanning electron microscopy (scale bar: 50 µm); (c) immunofluorescence staining of perilipin (red), LipidToxTM (green) and DAPI (blue) (scale bar: 50 µm). (d–f): Mature adipocytes in/from subcutaneous adipose tissue show unilocular lipid droplets from (d) semithin section from a resin-embedded biopsy-tissue, fixed with Karnovsky’s fixative and post-fixed with OsO4 stained with methylene blue/azurII; (e) immunofluorescence staining of a paraffin section from biopsied adipose tissue. Perilipin (red), DAPI (blue) (scale bar: 50 µm); (f) immunofluorescence staining of mature adipocytes isolated from liposuction material. LipidToxTM (green), DAPI (blue) (scale bar: 50 µm).