Disorders of Adipose Tissue and Lipodystrophies: Causes, Consequences, and Treatment Perspectives
DOI:
https://doi.org/10.12775/QS.2025.38.58194Keywords
Lipodystrophy, adipose tissue loss, metabolism, insulin resistance, diabetes, hypertriglyceridemia, HIV, metreleptin, adipogenesis, congenital lipodystrophy, acquired lipodystrophyAbstract
Lipodystrophies are rare metabolic disorders characterized by the loss of adipose tissue, which can manifest as generalized, partial, or localized. This condition is associated with metabolic complications such as insulin resistance, diabetes, hypertriglyceridemia, and liver steatosis. The paper discusses the classification of lipodystrophies by etiology and fat loss extent, including generalized and partial forms, both congenital and acquired. Special focus is placed on HIV-associated lipodystrophy due to the prevalence of antiretroviral therapy. The pathophysiology involves disrupted adipogenesis, leading to abnormal fat distribution and metabolic dysfunction. Diagnosis includes medical history, physical exams, and body composition analysis. Treatment focuses on managing metabolic issues and may involve therapies like metreleptin.
OBJECTIVE:
This study aims to analyze the pathophysiology, diagnosis, and treatment of lipodystrophies, particularly focusing on congenital, acquired, and HIV-associated forms. It explores the underlying metabolic mechanisms, diagnostic challenges, and current and future therapeutic approaches, including metreleptin and other strategies.
MATERIALS AND METHODS:
The study relies on scientific research, review articles, and reports on lipodystrophy syndromes, primarily sourced from PubMed, Google Scholar, and Cochrane Library. It examines data related to diagnostics, etiology, and treatment options.
CONCLUSIONS:
Lipodystrophies are rare and heterogeneous, making diagnosis challenging. Early detection is essential to prevent complications like diabetes and cardiovascular disease. Modern technologies such as dual-energy X-ray absorptiometry (DEXA) help assess body composition more accurately. Although therapies like metreleptin show promise, they remain expensive and difficult to implement. Further research is needed to improve understanding and management of lipodystrophies, and patient education is crucial for better outcomes.
References
[1] I. Hussain and A. Garg, “Lipodystrophy Syndromes,” Endocrinol Metab Clin North Am, vol. 45, no. 4, p. 783, Dec. 2016, doi: 10.1016/J.ECL.2016.06.012.
[2] L. Weng et al., “Surplus fatty acid synthesis increases oxidative stress in adipocytes and induces lipodystrophy,” Nat Commun, vol. 15, no. 1, p. 133, Dec. 2024, doi: 10.1038/S41467-023-44393-7.
[3] N. Patni and A. Garg, “Lipodystrophy for the Diabetologist—What to Look For,” Curr Diab Rep, vol. 22, no. 9, p. 461, Sep. 2022, doi: 10.1007/S11892-022-01485-W.
[4] N. Gupta et al., “Clinical Features and Management of Non-HIV–Related Lipodystrophy in Children: A Systematic Review,” J Clin Endocrinol Metab, vol. 102, no. 2, p. 363, Feb. 2016, doi: 10.1210/JC.2016-2271.
[5] S. Yang and C. Knox, “Prevalence of clinical characteristics of lipodystrophy in the US adult population in a healthcare claims database,” BMC Endocr Disord, vol. 24, no. 1, p. 102, Dec. 2024, doi: 10.1186/S12902-024-01629-X.
[6] P. Krüger, R. Hartinger, and K. Djabali, “Navigating Lipodystrophy: Insights from Laminopathies and Beyond,” Int J Mol Sci, vol. 25, no. 15, p. 8020, Aug. 2024, doi: 10.3390/IJMS25158020.
[7] R. J. Brown et al., “The diagnosis and management of lipodystrophy syndromes: A multi-society practice guideline,” Journal of Clinical Endocrinology and Metabolism, vol. 101, no. 12, pp. 4500–4511, Dec. 2016, doi: 10.1210/JC.2016-2466/SUPPL_FILE/JC-16-2466.PDF.
[8] G. Ceccarini, S. Magno, D. Gilio, C. Pelosini, and F. Santini, “Autoimmunity in lipodystrophy syndromes,” Presse Med, vol. 50, no. 3, p. 104073, Nov. 2021, doi: 10.1016/J.LPM.2021.104073.
[9] D. Araújo-Vilar and F. Santini, “Diagnosis and treatment of lipodystrophy: a step-by-step approach,” J Endocrinol Invest, vol. 42, no. 1, p. 61, Jan. 2018, doi: 10.1007/S40618-018-0887-Z.
[10] M. Le Nguyen et al., “Leptin Attenuates Cardiac Hypertrophy in Patients With Generalized Lipodystrophy,” J Clin Endocrinol Metab, vol. 106, no. 11, p. e4327, Nov. 2021, doi: 10.1210/CLINEM/DGAB499.
[11] L. T. Fourman and S. K. Grinspoon, “Approach to the Patient With Lipodystrophy,” J Clin Endocrinol Metab, vol. 107, no. 6, p. 1714, Jun. 2022, doi: 10.1210/CLINEM/DGAC079.
[12] J. Von Schnurbein et al., “European lipodystrophy registry: background and structure,” Orphanet J Rare Dis, vol. 15, no. 1, p. 17, Jan. 2020, doi: 10.1186/S13023-020-1295-Y.
[13] J. L. Finkelstein, P. Gala, R. Rochford, M. J. Glesby, and S. Mehta, “HIV/AIDS and lipodystrophy: Implications for clinical management in resource-limited settings,” J Int AIDS Soc, vol. 18, no. 1, p. 19033, Jan. 2015, doi: 10.7448/IAS.18.1.19033.
[14] T. A. Lamesa, “Biological Depiction of Lipodystrophy and Its Associated Challenges Among HIV AIDS Patients: Literature Review,” HIV AIDS (Auckl), vol. 16, p. 123, 2024, doi: 10.2147/HIV.S445605.
[15] V. Behera, M. Randive, S. Sundaray, and M. S. N. Murty, “Antiretroviral therapy-induced lipodystrophy,” BMJ Case Rep, vol. 2015, p. bcr2014207090, Feb. 2015, doi: 10.1136/BCR-2014-207090.
[16] S. S. Bhimji and R. A. Whitten, “HIV-Associated Lipodystrophy,” StatPearls, Nov. 2022, Accessed: Jan. 08, 2025. [Online]. Available: https://www.ncbi.nlm.nih.gov/books/NBK493183/
[17] M. M. D. Romano, P. A. I. Chacon, F. N. Z. Ramalho, M. C. Foss, and A. Schmidt, “Cardiac Alterations in Patients with Familial Lipodystrophy,” Arq Bras Cardiol, vol. 114, no. 2, p. 305, Feb. 2020, doi: 10.36660/ABC.20190016.
[18] N. B. da Cunha Olegario et al., “Identifying congenital generalized lipodystrophy using deep learning-DEEPLIPO,” Sci Rep, vol. 13, no. 1, p. 2176, Dec. 2023, doi: 10.1038/S41598-023-27987-5.
[19] A. Gambineri and L. Zanotti, “Polycystic ovary syndrome in familial partial lipodystrophy type 2 (FPLD2): basic and clinical aspects,” Nucleus, vol. 9, no. 1, p. 392, Jan. 2018, doi: 10.1080/19491034.2018.1509659.
[20] A. J. Eldin et al., “Cardiac phenotype in familial partial lipodystrophy,” Clin Endocrinol (Oxf), vol. 94, no. 6, p. 1043, Jun. 2021, doi: 10.1111/CEN.14426.
[21] A. Fernández-Pombo, S. Sánchez-Iglesias, S. Cobelo-Gómez, Á. Hermida-Ameijeiras, and D. Araújo-Vilar, “Familial partial lipodystrophy syndromes,” Presse Med, vol. 50, no. 3, p. 104071, Nov. 2021, doi: 10.1016/J.LPM.2021.104071.
[22] F. Mainieri and F. Chiarelli, “Lipodystrophies in Children,” Horm Res Paediatr, vol. 95, no. 4, pp. 305–320, Oct. 2022, doi: 10.1159/000522620.
[23] C. Mandel-Brehm et al., “Autoantibodies to Perilipin-1 Define a Subset of Acquired Generalized Lipodystrophy,” Diabetes, vol. 72, no. 1, p. 59, Jan. 2022, doi: 10.2337/DB21-1172.
[24] S. Özen, B. Akıncı, and E. A. Oral, “Current Diagnosis, Treatment and Clinical Challenges in the Management of Lipodystrophy Syndromes in Children and Young People,” J Clin Res Pediatr Endocrinol, vol. 12, no. 1, pp. 17–28, 2020, doi: 10.4274/JCRPE.GALENOS.2019.2019.0124.
[25] N. Patni, C. Chard, D. Araújo-Vilar, H. Phillips, D. A. Magee, and B. Akinci, “Diagnosis, treatment and management of lipodystrophy: the physician perspective on the patient journey,” Orphanet J Rare Dis, vol. 19, no. 1, p. 263, Dec. 2024, doi: 10.1186/S13023-024-03245-3.
[26] C. A. Meehan, E. Cochran, A. Kassai, R. J. Brown, and P. Gorden, “Metreleptin for injection to treat the complications of leptin deficiency in patients with congenital or acquired generalized lipodystrophy,” Expert Rev Clin Pharmacol, vol. 9, no. 1, p. 59, Jan. 2015, doi: 10.1586/17512433.2016.1096772.
[27] C. Vigouroux, H. Mosbah, and C. Vatier, “Leptin replacement therapy in the management of lipodystrophy syndromes,” Ann Endocrinol (Paris), vol. 85, no. 3, pp. 201–204, Jun. 2024, doi: 10.1016/J.ANDO.2024.05.022.
[28] A. Roumane, G. D. Mcilroy, N. Sommer, W. Han, L. K. Heisler, and J. J. Rochford, “GLP-1 receptor agonist improves metabolic disease in a pre-clinical model of lipodystrophy,” Front Endocrinol (Lausanne), vol. 15, p. 1379228, 2024, doi: 10.3389/FENDO.2024.1379228/FULL.
[29] R. J. Brown et al., “Lymphoma in acquired generalized lipodystrophy,” Leuk Lymphoma, vol. 57, no. 1, p. 45, Jan. 2015, doi: 10.3109/10428194.2015.1040015.
[30] S. Bindlish, L. S. Presswala, and F. Schwartz, “Lipodystrophy: Syndrome of severe insulin resistance,” Postgrad Med, vol. 127, no. 5, pp. 511–516, Jan. 2015, doi: 10.1080/00325481.2015.1015927.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Kamila Rosińska, Ewelina Justyna Janicka, Julia Natalia Skibicka, Monika Niedźwiedzka, Mateusz Rosiński
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Stats
Number of views and downloads: 38
Number of citations: 0
