Lipodystrophy: metabolic insights from a rare disorder
Abstract
Obesity, insulin resistance and their attendant complications are among the leading causes of morbidity and premature mortality today, yet we are only in the early stages of understanding the molecular pathogenesis of these aberrant phenotypes. A powerful approach has been the study of rare patients with monogenic syndromes that manifest as extreme phenotypes. For example, there are striking similarities between the biochemical and clinical profiles of individuals with excess fat (obesity) and those with an abnormal paucity of fat (lipodystrophy), including severe insulin resistance, dyslipidaemia, hepatic steatosis and features of hyperandrogenism. Rare lipodystrophy patients therefore provide a tractable genetically defined model for the study of a prevalent human disease phenotype. Indeed, as we review herein, detailed study of these syndromes is beginning to yield valuable insights into the molecular genetics underlying different forms of lipodystrophy, the essential components of normal adipose tissue development and the mechanisms by which disturbances in adipose tissue function can lead to almost all the features of the metabolic syndrome.
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Patients with acquired generalized lipodystrophy lose fat from large areas of the body during childhood and adolescence and often have hepatic steatosis.
“Patients with acquired generalized lipodystrophy lose fat from large areas of the body during childhood and adolescence and often have hepatic steatosis (100).”
From Evaluation and Treatment of Hypertriglyceridemia: An Endocrine Society Clinical Practice Guideline (2012) · cites this paper as [100]
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Semple, R. K., Savage, D. B., Halsall, D. J., & O’Rahilly, S. (2010) · Elsevier eBooks · doi:10.1016/b978-0-12-374430-2.00004-3 · Cited by 14 · see citing works
Self-citation
Flagged first, then by citations
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Evaluation and Treatment of Hypertriglyceridemia: An Endocrine Society Clinical Practice Guideline
Berglund, L., Brunzell, J. D., Goldberg, A. C., Goldberg, I. J., Sacks, F., Murad, M. H., & Stalenhoef, A. F. H. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-3213 · Cited by 887 · see citing works
Zhu, L., Brown, W. C., Cai, Q., Krust, A., Chambon, P., McGuinness, O. P., & Stafford, J. M. (2013) · Diabetes · doi:10.2337/db11-1718 · Cited by 326 · see citing works
HIV infection and cardiovascular disease
Hemkens, L. G., & Bucher, H. C. (2014) · European Heart Journal · doi:10.1093/eurheartj/eht528 · Cited by 251 · see citing works
Adipose tissue and metabolic syndrome: too much, too little or neither
Grundy, S. M. (2015) · European Journal of Clinical Investigation · doi:10.1111/eci.12519 · Cited by 187 · see citing works
Differential Roles of Insulin and IGF-1 Receptors in Adipose Tissue Development and Function
Boucher, J., Softic, S., El Ouaamari, A., Krumpoch, M. T., Kleinridders, A., Kulkarni, R. N., O’Neill, B. T., & Kahn, C. R. (2016) · Diabetes · doi:10.2337/db16-0212 · Cited by 154 · see citing works
Osteocytes Regulate Primary Lymphoid Organs and Fat Metabolism
Sato, M., Asada, N., Kawano, Y., Wakahashi, K., Minagawa, K., Kawano, H., Sada, A., Ikeda, K., Matsui, T., & Katayama, Y. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.09.014 · Cited by 126 · see citing works
Lipoatrophy and metabolic disturbance in mice with adipose-specific deletion of kindlin-2
Gao, H., Guo, Y., Yan, Q., Yang, W., Li, R., Lin, S., Bai, X., Liu, C., Chen, D., Cao, H., et al. (2019) · JCI Insight · doi:10.1172/jci.insight.128405 · Cited by 53 · see citing works
“For example, patients suffering from congenital generalized lipodystrophy usually develop insulin resistance, hypertriglyceridemia, and fatty liver (7, 8).”
BackgroundAdamski, K., Cook, K., Gupta, D., Morris, E., Tuttle, E., Carr, E., Cremasco, F., Cochran, E., & Brown, R. J. (2021) · Current Medical Research and Opinion · doi:10.1080/03007995.2021.1976125 · Cited by 11 · see citing works
- Authors
- Huang-Doran, I., Sleigh, A., Rochford, J. J., O'Rahilly, S., & Savage, D. B.
- Affiliations
- University of Cambridge (GB)
- Wellcome/MRC Institute of Metabolic Science (GB)
- Venue
- Journal of Endocrinology
- Publisher
- Bioscientifica
- Published
- 2010-09-24
- Volume
- 207
- Issue
- 3
- Pages
- 245-255
- ISSN
- 0022-0795 (ISSN-L)
- 1479-6805
- OpenAlex
- W2166938485
- Cited by
- 215
- References
- 94
- Citations by year
- 2026: 2 · 2025: 9 · 2024: 9 · 2023: 11 · 2022: 13 · 2021: 8 · 2020: 14 · 2019: 13 · 2018: 22 · 2017: 19 · 2016: 14 · 2015: 13 · 2014: 15 · 2013: 20 · 2012: 17
- FWCI
- 12.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- GlaxoSmithKline
- Wellcome Trust (091551, 078986/Z/06/Z)
- National Institute for Health and Care Research
- Medical Research Council
- NIHR Cambridge Biomedical Research Centre
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- lipodystrophy, obesity, insulin resistance, metabolic syndrome, monogenic disorders, adipose tissue development, dyslipidemia, hepatic steatosis, hyperandrogenism, molecular genetics, rare genetic disorders
- MeSH terms
- Adipose Tissue, Animals, Fatty Liver, Female, Humans, Insulin Resistance, Lipodystrophy, Male, Obesity, Gene Expression, Hyperandrogenism, Metabolic Syndrome, Dyslipidemias, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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