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  • Review Article
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Lipodystrophy: pathophysiology and advances in treatment

Nature Reviews Endocrinology volume 7, pages 137–150 (2011)Cite this article

Subjects

Abstract

Lipodystrophy is a medical condition characterized by complete or partial loss of adipose tissue. Not infrequently, lipodystrophy occurs in combination with pathological accumulation of adipose tissue at distinct anatomical sites. Patients with lipodystrophy exhibit numerous metabolic complications, which indicate the importance of adipose tissue as an active endocrine organ. Not only the total amount but also the appropriate distribution of adipose tissue depots contribute to the metabolic state. Genetic and molecular research has improved our understanding of the mechanisms underlying lipodystrophy. Circulating levels of hormones secreted by the adipose tissue, such as leptin and adiponectin, are greatly reduced in distinct subpopulations of patients with lipodystrophy. This finding rationalizes the use of these adipokines or of agents that increase their circulating levels, such as peroxisome proliferator-activated receptor γ (PPARγ) agonists, for therapeutic purposes. Other novel therapeutic approaches, including the use of growth hormone and growth-hormone-releasing factors, are also being studied as potential additions to the therapeutic armamentarium. New insights gained from research and clinical trials could potentially revolutionize the management of this difficult-to-treat condition.

Key Points

  • Lipodystrophy is characterized by complete or partial loss of adipose tissue (lipoatrophy) that can occur in conjunction with pathological accumulation of adipose tissue (lipohypertrophy) in other regions of the body

  • Patients with lipodystrophy suffer from numerous metabolic complications, which shows the importance of adipose tissue as an active endocrine organ

  • Not only the total amount but also the distribution of adipose tissue depots contribute to the metabolic state

  • Lipodystrophy can be inherited or acquired, although inherited lipodystrophy syndromes are exceedingly rare

  • Currently, the most prevalent type of lipodystrophy is an acquired form that occurs among HIV-infected individuals treated with highly active antiretroviral therapy

  • Circulating levels of adipokines are greatly reduced in distinct subpopulations of patients with lipodystrophy, rationalizing the use of these hormones or of agents that increase their concentrations for therapeutical purposes

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Figure 1: Adipose tissue redistribution in HIV-infected patients on highly active antiretroviral therapy.

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Acknowledgements

C. S. Mantzoros is supported by grants DK-58785, DK-79929, DK-081913 and AG-032030 from the NIH. His work on HIV-related lipodystrophy has been supported by the American Diabetes Association.

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  1. Division of Endocrinology, Diabetes & Metabolism, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Feldberg 875, Boston, 02215, MA, USA

    Christina G. Fiorenza & Sharon H. Chou

  2. Section of Endocrinology, Veteran Affairs Boston Healthcare System and Harvard Medical School, Boston, 02130, MA, USA

    Christos S. Mantzoros

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C. G. Fiorenza and S. H. Chou researched the data for the article. All authors provided a substantial contribution to discussions of the content, contributed equally to writing the article and reviewed and/or edited the manuscript before submission.

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Correspondence to Christos S. Mantzoros.

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C. S. Mantzoros declares an association with the following company: Amylin (grant/research support). The other authors declare no competing interests.

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Fiorenza, C., Chou, S. & Mantzoros, C. Lipodystrophy: pathophysiology and advances in treatment. Nat Rev Endocrinol 7, 137–150 (2011). https://doi.org/10.1038/nrendo.2010.199

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