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Current Mechanistic Understandings of Lymphedema and Lipedema 2.0
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Current Mechanistic Understandings of Lymphedema and Lipedema 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (28 February 2023) | Viewed by 5347

Special Issue Editor

Dr. Joseph M. Rutkowski

E-Mail Website
Guest Editor
Department of Medical Physiology, College of Medicine, Texas A&M University, Bryan, TX 77807, USA
Interests: lymphatic physiology; metabolic systems; metabolite transport; whole animal metabolism; endocrinology; adipose tissue; lymphatic system; lymphangiogenesis; biology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

While the external presentation of lymphedema and lipedema may appear similar, the diagnosis and molecular mechanisms underlying these conditions are quite varied. Lymphedema results from a genetic or acquired lymphatic deficiency, causing fluid accumulation, inflammation, and adipose tissue expansion. The pathological adipose expansion in lipedema, however, arises from an etiology that is yet to be well defined but potentially includes blood microvascular and lymphatic insufficiency, altered extracellular matrix composition, and dysfunctional adipose biology. It will be important to define how these traditionally understudied diseases are similar and yet distinct in order to meet their unique needs in terms of diagnostics and treatment options.

This Special Issue will publish original articles as well as full reviews that cover the current understanding and molecular and physiological mechanisms that are shared between, and importantly, unique to either lymphedema and lipedema. Manuscripts need not cover both pathologies, but rather should present novel findings about early diagnostics and molecular mechanisms defining what we know and the key remaining questions.

Dr. Joseph M. Rutkowski
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • lymphedema
  • lipedema
  • angiogenesis
  • lymphangiogenesis
  • vascular malformations
  • obesity
  • adipogenesis
  • extracellular matrix
  • inflammation
  • pain

Published Papers (2 papers)

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Research

14 pages, 3598 KiB  
Article
A Comparative Analysis to Dissect the Histological and Molecular Differences among Lipedema, Lipohypertrophy and Secondary Lymphedema
by Julia von Atzigen, Anna Burger, Lisanne Grünherz, Carlotta Barbon, Gunther Felmerer, Pietro Giovanoli, Nicole Lindenblatt, Stefan Wolf and Epameinondas Gousopoulos
Int. J. Mol. Sci. 2023, 24(8), 7591; https://doi.org/10.3390/ijms24087591 - 20 Apr 2023
Cited by 5 | Viewed by 2428
Abstract
Lipedema, lipohypertrophy and secondary lymphedema are three conditions characterized by disproportionate subcutaneous fat accumulation affecting the extremities. Despite the apparent similarities and differences among their phenotypes, a comprehensive histological and molecular comparison does not yet exist, supporting the idea that there is an [...] Read more.
Lipedema, lipohypertrophy and secondary lymphedema are three conditions characterized by disproportionate subcutaneous fat accumulation affecting the extremities. Despite the apparent similarities and differences among their phenotypes, a comprehensive histological and molecular comparison does not yet exist, supporting the idea that there is an insufficient understanding of the conditions and particularly of lipohypertrophy. In our study, we performed histological and molecular analysis in anatomically-, BMI- and gender-matched samples of lipedema, lipohypertrophy and secondary lymphedema versus healthy control patients. Hereby, we found a significantly increased epidermal thickness only in patients with lipedema and secondary lymphedema, while significant adipocyte hypertrophy was identified in both lipedema and lipohypertrophy. Interestingly, the assessment of lymphatic vessel morphology showed significantly decreased total area coverage in lipohypertrophy versus the other conditions, while VEGF-D expression was significantly decreased across all conditions. The analysis of junctional genes often associated with permeability indicated a distinct and higher expression only in secondary lymphedema. Finally, the evaluation of the immune cell infiltrate verified the increased CD4+ cell and macrophage infiltration in lymphedema and lipedema respectively, without depicting a distinct immune cell profile in lipohypertrophy. Our study describes the distinct histological and molecular characteristics of lipohypertrophy, clearly distinguishing it from its two most important differential diagnoses. Full article
(This article belongs to the Special Issue Current Mechanistic Understandings of Lymphedema and Lipedema 2.0)
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16 pages, 4274 KiB  
Article
Indications of Peripheral Pain, Dermal Hypersensitivity, and Neurogenic Inflammation in Patients with Lipedema
by Adri Chakraborty, Rachelle Crescenzi, Timaj A. Usman, Andrea J. Reyna, Maria E. Garza, Sara Al-Ghadban, Karen L. Herbst, Paula M. C. Donahue and Joseph M. Rutkowski
Int. J. Mol. Sci. 2022, 23(18), 10313; https://doi.org/10.3390/ijms231810313 - 7 Sep 2022
Cited by 11 | Viewed by 2588
Abstract
Lipedema is a disease with abnormally increased adipose tissue deposition and distribution. Pain sensations have been described in the clinical evaluation of lipedema, but its etiology remains poorly understood. We hypothesized that pain sensitivity measurements and ex vivo quantitation of neuronal cell body [...] Read more.
Lipedema is a disease with abnormally increased adipose tissue deposition and distribution. Pain sensations have been described in the clinical evaluation of lipedema, but its etiology remains poorly understood. We hypothesized that pain sensitivity measurements and ex vivo quantitation of neuronal cell body distribution in the skin would be lipedema stage-dependent, and could, thus, serve to objectively characterize neuropathic pain in lipedema. The pain was assessed by questionnaire and peripheral cutaneous mechanical sensitization (von-Frey) in lipedema (n = 27) and control (n = 23) consenting female volunteers. Dermal biopsies from (n = 11) Stages 1–3 lipedema and control (n = 10) participants were characterized for neuronal cell body and nociceptive neuropeptide calcitonin gene-related peptide (CGRP) and nerve growth factor (NGF) distribution. Stage 2 or 3 lipedema participants responded positively to von Frey sensitization in the calf and thigh, and Stage 3 participants also responded in the arm. Lipedema abdominal skin displayed reduced Tuj-1+ neuronal cell body density, compared to healthy controls, while CGRP and NGF was significantly elevated in Stage 3 lipedema tissues. Together, dermal neuronal cell body loss is consistent with hyper-sensitization in patients with lipedema. Further study of neuropathic pain in lipedema may elucidate underlying disease mechanisms and inform lipedema clinical management and treatment impact. Full article
(This article belongs to the Special Issue Current Mechanistic Understandings of Lymphedema and Lipedema 2.0)
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