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Inicio Endocrinología y Nutrición Lipodistrofias: bases moleculares y manifestaciones clínicas
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Vol. 50. Núm. 4.
Páginas 133-144 (abril 2003)
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Vol. 50. Núm. 4.
Páginas 133-144 (abril 2003)
Acceso a texto completo
Lipodistrofias: bases moleculares y manifestaciones clínicas
Lipodystrophies: molecular basis and clinical features
Visitas
19756
D. araÚjo Vilar
Autor para correspondencia
david.araujo@ya.com

Correspondencia: Dr. David Araújo Vilar. Servicio de Endocrinoloxía e Nutrición. Hospital Clínico Universitario de Santiago. Tv. Choupana s/n. 15706 Santiago de Compostela. España.
Servicio de Endocrinoloxía e Nutrición. Hospital Clínico Universitario de Santiago de Compostela. Departamento de Medicina. Universidade de Santiago de Compostela. España
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Información del artículo

Las lipodistrofias son trastornos poco frecuentes que afectan al tejido adiposo, principalmente al metabólicamente activo, tanto subcutáneo como visceral, y que se caracterizan por la desaparición del mismo. La pérdida de tejido adiposo puede afectar a la práctica totalidad del mismo –como en las lipodistrofias generalizadas– o sólo a una parte –como en las lipodistrofias parciales y localizadas–. Las lipodistrofias pueden ser genéticas o adquiridas, y estas últimas suelen tener una base inmunológica. Con relativa frecuencia y generalmente debido a la extensa pérdida de tejido adiposo, las lipodistrofias se asocian a una serie de complicaciones metabólicas como son la resistencia a la insulina, la hipertrigliceridemia, el descenso del colesterol HDL y la hipoleptinemia. También es frecuente la asociación con la acantosis nigricans, la esteatosis hepática y el síndrome del ovario poliquístico. Esta revisión tiene como objetivo describir las características clínicas y los criterios diagnósticos de los distintos tipos de lipodistrofias y profundizar en las bases moleculares de las mismas.

Palabras clave:
Tejido adiposo
Resistencia a la insulina
Hipertrigliceridemia
Laminina A/C
Gen LMNA

Lipodystrophies are rare diseases which affect adipose tissue, usually metabolically active tissue, both subcutaneous and visceral, and which are characterized by fat loss. This loss of fat can affect almost the entire body, as in generalized lipodystrophies, or only part of the body, as in partial and localized lipodystrophies. The causes of lipodystrophies can be genetic or acquired, and the latter usually have an immunological basis.

Lipodystrophies are frequently associated with a series of metabolic complications such as insulin resistance, hypertriglyceridemia, low HDLcholesterol and hypoleptinemia, which are usually related to the extent of fat loss. Acanthosis nigricans, hepatic steatosis and polycystic ovaries are also frequently associated. The aim of this review is to describe the clinical features and diagnostic criteria of the different types of lipodystrophies, as well as to provide further information on their molecular bases.

Key words:
Adipose tissue
Insulin resistance
Hypertriglyceridemia
Lamin A/C
LMNA gene
El Texto completo está disponible en PDF
Bibliografía
[1.]
H. Cao, R.A. Hegele.
Nuclear lamin A/C R482Q mutation in Canadian kindreds with Dunnigan-type familial partial lipodystrophy.
Hum Mol Genet, 9 (2000), pp. 109-112
[2.]
A. Carr, D.A. Cooper.
Adverse effects of antiretroviral therapy.
Lancet, 356 (2000), pp. 1423-1430
[3.]
A. Garg, J.L. Fleckenstein, R.M. Peshock, S.M. Grundy.
Peculiar distribution of adipose tissue in patients with congenital generalized lipodystrophy.
J Clin Endocrinol Metab, 75 (1992), pp. 358-361
[4.]
E.A. Oral, V. Simha, E. Ruiz, A. Andewelt, A. Premkumar, P. Snell, et al.
Leptin-replacement therapy for lipodystrophy.
N Engl J Med, 346 (2002), pp. 570-578
[5.]
D.J. Lloyd, R.C. Trembath, S. Shackleton.
A novel interaction between lamin A and SREBP1: implications for partial lipodystrophy and other laminopathies.
Hum Mol Genet, 11 (2002), pp. 769-777
[6.]
C. Vigouroux, M. Auclair, E. Dubosclard, M. Pouchelet, J. Capeau, J.C. Courvalin, et al.
Nuclear envelope disorganization in fibroblasts from lipodystrophic patients with heterozygous R482Q/W mutations in the lamin A/C gene.
J Cell Sci, 114 (2001), pp. 4459-4468
[7.]
W. Berardinelli.
An undiagnosed endocrinometabolic syndrome: report of two cases.
J Clin Endocrinol Metab, 14 (1954), pp. 193-204
[8.]
M. Seip.
Lipodystrophy and gigantism with associated endocrine manifestations: a new diencephalic syndrome?.
Acta Paediatr, 48 (1959), pp. 555-574
[9.]
M.G. Dunnigan, M.A. Cochrane, A. Kelly, J.W. Scott.
Familial lipoatrophic with dominant transmission.
Quarterly Journal of Medicine, 43 (1974), pp. 33-48
[10.]
J. Köbberling, B. Willms, R. Kattermann, W. Creutzfeldt.
Lipodystrophy of the extremities. A dominantly inherited syndrome associated with lipoatrophic diabetes.
Humangenetik, 29 (1975), pp. 111-120
[11.]
F.L. Ozer, J.R. Lichtenstein, P.O. Kwiterovich Jr, V.A. McKusick.
New genetic variety of lipodystrophy.
Clin Res, 21 (1973), pp. 533
[12.]
L.W. Young, J.F. Radebaugh, P. Rubin.
New syndrome manifested by mandibular hypoplasia, acroosteolysis, stiff joints and cutaneous atrophy (mandibuloacral dysplasia) in two unrelated boys.
The clinical delineation of birth defects: orofacial structures, pp. 291-293
[13.]
R.D. Lawrence.
Lipodystrophy and hepatomegaly with diabetes, lipemia, and other metabolic disturbances.
Lancet, (1946), pp. 724-731
[14.]
L. Barraquer.
Histoire clinique d'un cas d'atrophie du tissu celluloadipeux.
Neurolog Zentralblatt, 26 (1907), pp. 1072
[15.]
A. Simons.
Eine seltnen Trophoneurose: “Lipodystrophia progressiva” Z.
Ges Neurol Psychiat, 5 (1911), pp. 29-38
[16.]
A. Garg.
Lipodystrophies.
Am J Med, 108 (2000), pp. 143-152
[17.]
A.K. Agarwal, E. Arioglu, S. de Almeida, N. Akkoc, S.I. Taylor, A.M. Bowcock, et al.
AGPAT2 is mutated in congenital generalized lipodystrophy linked to chromosome 9q34.
Nat Genet, 31 (2002), pp. 21-23
[18.]
J. Magre, M. Delepine, E. Khallouf, T. Gedde-Dahl Jr, L. Van Maldergem, E. Sobel, et al.
Identification of the gene altered in Berardinelli-Seip congenital lipodystrophy on chromosome 11q13.
Nat Genet, 28 (2001), pp. 365-370
[19.]
A. Garg, D. Parsons, J. Stray-Gundersen, L.A. Bertocci.
Skeletal muscle morphology and exercise response in congenital generalized lipodystrophy.
Diabetes Care, 23 (2000), pp. 1545-1550
[20.]
V.C. Pardini, I.M. Victoria, S.M. Rocha, D.G. Andrade, A.M. Rocha, F.B. Pieroni, et al.
Leptin levels, beta-cell function, and insulin sensitivity in families with congenital and acquired generalized lipoatrophic diabetes.
J Clin Endocrinol Metab, 83 (1998), pp. 503-508
[21.]
M. Chandalia, A. Garg, F. Vuitch, F. Nizzi.
Postmortem findings in congenital generalized lipodystrophy.
J Clin Endocrinol Metab, 80 (1995), pp. 3077-3081
[22.]
C. Vigouroux, E. Khallouf, C. Bourut, J.J. Robert, M. de Kerdanet, N. Tubiana-Rufi, et al.
Genetic exclusion of 14 candidates genes in lipoatrophic diabetes using linkage analysis in 10 consanguineous families.
J Clin Endocrinol Metab, 82 (1997), pp. 3438-3444
[23.]
C. Vigouroux, J. Magre, M.C. Vantyghem, C. Bourut, O. Lascols, S. Shackleton, et al.
Lamin A/C gene: sex-determined expression of mutations in Dunnigan-type familial partial lipodystrophy and absence of coding mutations in congenital and acquired generalized lipoatrophy.
Diabetes, 49 (2000), pp. 1958-1962
[24.]
A. Garg, R. Wilson, R. Barnes, E. Arioglu, Z. Zaidi, F. Gurakan, et al.
A gene for congenital generalized lipodystrophy maps to human chromosome 9q34.
J Clin Endocrinol Metab, 84 (1999), pp. 3390-3394
[25.]
K. Heathcote, A. Rajab, J. Magre, P. Syrris, M. Besti, M. Patton, et al.
Molecular analysis of Berardinelli-Seip congenital lipodystrophy in Iman: evidence for multiple loci.
Diabetes, 51 (2002), pp. 1291-1293
[26.]
D. Araujo-Vilar, L. Loidi, F. Dominguez, J. Cabezas-Cerrato.
Phenotypic gender differences in subjects with familial partial lipodystrophy (Dunnigan variety) due to a nuclear lamin A/C R482W mutation.
[en prensa] Horm Metab Res, (2003),
[27.]
R.A. Speckman, A. Garg, F. Du, L. Bennett, R. Veile, E. Arioglu, et al.
Mutational and haplotype analyses of familial partial lipodystrophy (Dunnigan variety) reveal recurrent missense mutations in the globular C-terminal domain of lamin A/C.
Am J Hum Genet, 66 (2000), pp. 1192-1198
[28.]
A. Garg, R.M. Peshock, J.L. Fleckenstein.
Adipose tissue distribution pattern in patients with familial partial lipodystrophy (Dunnigan variety).
J Clin Endocrinol Metab, 84 (1999), pp. 170-174
[29.]
J. Kobberling, M.G. Dunnigan.
Familial partial lipodystrophy: two types of an X linked dominant syndrome, lethal in the hemizygous state.
J Med Genet, 23 (1986), pp. 120-127
[30.]
W.A. Haque, I. Shimomura, Y. Matsuzawa, A. Garg.
Serum adiponectin and leptin levels in patients with lipodystrophies.
J Clin Endocrinol Metab, 87 (2002), pp. 2395
[31.]
M.J.M. Ursich, R.T. Fukui, M.A.S. Galvao, J.A. Marcondes, A.T. Santomauro, M.E. Silva, et al.
Insulin resistance in limb and trunk partial lipodystrophy (type 2 Kobberling-Dunnigan syndrome).
Metabolism, 46 (1997), pp. 159-163
[32.]
H.H. Schmidt, J. Genschel, P. Baier, M. Schmidt, J. Ockenga, U.J. Tietge, et al.
Dyslipemia in familial partial lipodystrophy caused by an R482W mutation in the LMNA gene.
J Clin Endocrinol Metab, 86 (2001), pp. 2289-2295
[33.]
M.B. Davison, R.T. Young.
Metabolic studies in familial partial lipodystrophy of the lower trunk and extremities.
Diabetologia, 11 (1975), pp. 561-568
[34.]
J. Burn, M. Baraitser.
Partial lipoatrophy with insulin resistant diabetes and hyperlipidaemia (Dunnigan syndrome).
J Med Genet, 23 (1986), pp. 128-130
[35.]
R.A. Hegele, C.M. Anderson, J. Wang, D.C. Jones, H. Cao.
Association between nuclear lamin A/C R482Q mutation and partial lipodystrophy with hyperinsulinemia, dyslipidemia, hypertension, and diabetes.
Genome Res, 10 (2000), pp. 652-658
[36.]
R.A. Hegele.
Premature atherosclerosis associated with monogenic insulin resistance.
Circulation, 103 (2001), pp. 2225-2229
[37.]
R.A. Hegele.
Molecular basis of partial lipodystrophy and prospects for therapy.
Trends Mol Med, 7 (2001), pp. 121-126
[38.]
A. Garg.
Gender differences in the prevalence of metabolic complications in familial partial lipodystrophy (Dunnigan variety).
J Clin Endocrinol Metab, 85 (2000), pp. 1776-1782
[39.]
G. Bonne, M.R. Di Barletta, S. Varnous, H.M. Becane, E.H. Hammouda, L. Merlini, et al.
Mutations in the gene encoding lamin A/C cause autosomal dominant Emery-Dreifuss muscular dystrophy.
Nat Genet, 21 (1999), pp. 285-288
[40.]
D. Fatkin, C. MacRae, T. Sasaki, M.R. Wolff, M. Porcu, M. Frenneaux, et al.
Missense mutations in the rod domain of the lamin A/C gene as causes of dilated cardiomyopathy and conduction-system disease.
N Engl J Med, 341 (1999), pp. 1715-1724
[41.]
R.A. Hegele, H. Cao, C.M. Anderson, I.M. Hramiak.
Heterogeneity of nuclear lamin A mutations in Dunnigan-type familial partial lipodystrophy.
J Clin Endocrinol Metab, 85 (2000), pp. 3431-3435
[42.]
A. Garg, R.A. Speckman, A.M. Bowcock.
Multisystem dystrophy syndrome due to novel missense mutations in the amino-terminal head and alpha-helical rod domains of the lamin A/C gene.
Am J Med, 112 (2002), pp. 549-555
[43.]
A. Garg, M. Vinaitheerthan, P.T. Weatherall, A.N. Bowcock.
Phenotypic heterogeneity in patients with familial partial lipodystrophy (Dunnigan variety) related to the site of missense mutations in lamin A/C gene.
J Clin Endocrinol Metab, 86 (2001), pp. 59-65
[44.]
C.J. Hutchison, M. Alvarez-Reyes, O.A. Vaughan.
Lamins in disease: why do ubiquitously expressed nuclear envelope proteins give rise to tissue-specific disease phenotypes?.
J Cell Sci, 114 (2001), pp. 9-19
[45.]
I. Shimomura, R.E. Hammer, S. Ikemoto, M.S. Brown, J.L. Goldstein.
Leptin reverses insulin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy.
Nature, 401 (1999), pp. 73-76
[46.]
D.J. Lloyd, R.C. Trembath, S. Shackleton.
A novel interaction between lamin A and SREBP1: implications for partial lipodystrophy and other laminopathies.
Hum Mol Genet, 11 (2002), pp. 769-777
[47.]
G. Novelli, A. Muchir, F. Sangiuolo, A. Helbling-Leclerc, M.R. D'Apice, C. Massart, et al.
Mandibuloacral dysplasia is caused by a mutation in LMNA-encoding lamin A/C.
Am J Hum Genet, 71 (2002), pp. 426-431
[48.]
V. Simha, A. Garg.
Body fat distribution and metabolic derangements in patients with familial partial lipodystrophy associated with mandibuloacral dysplasia.
J Clin Endocrinol Metab, 87 (2002), pp. 776-785
[49.]
J.R. Berger, E.A. Oral, S.I. Taylor.
Familial lipodystropy associated with neurodegeneration and congenital cataracts.
Neurology, 58 (2002), pp. 43-47
[50.]
A.K. Agarwal, A. Garg.
A novel heterozygous mutation in peroxisome proliferator-activated receptor-γ gene in a patient with familial partial lipodystrophy.
J Clin Endocrinol Metab, 87 (2002), pp. 408-411
[51.]
L.H. Ziegler.
Lipodystrophies: report of seven cases.
Brain, 51 (1928), pp. 145-167
[52.]
R.D. Lawrence.
Lipodystrophy and hepatomegaly with diabetes, lipemia, and other metabolic disturbances.
Lancet, i (1946), pp. 724-731
[53.]
C. Bolan, E.A. Oral, P. Gorden, S. Taylor, S.F. Leitman.
Intensive, long-term plasma exchange therapy for severe hypertriglyceridemia in acquired generalized lipoatrophy.
J Clin Endocrinol Metab, 87 (2002), pp. 380-384
[54.]
B.K. Dolberg, M.J. Lenhard.
Successful outcome of pregnancy in a patient with generalized lipoatrophic diabetes mellitus.
Endocr Pract, 6 (2000), pp. 34-36
[55.]
J.K. Billings, S.S. Milgraum, A.K. Gupta, J.T. Headington, J.E. Rasmussen.
Lipoatrophic panniculitis: a possible autoimmune inflammatory disease of fat.
Arch Dermatol, 123 (1987), pp. 1662-1666
[56.]
J.M. Edge, D.B. Dunger, M.J. Dillon.
Weber-Christian panniculitis and chronic active hepatitis.
Eur J Pediatr, 145 (1986), pp. 227-229
[57.]
T. Sasaki, H. Ono, H. Nakajima, J. Sugimoto.
Lipoatrophic diabetes.
J Dermatol, 19 (1992), pp. 246-249
[58.]
A. Hubler, K. Abendroth, T. Keiner, W. Stocker, E. Kauf, G. Hein, et al.
Dysregulation of insulin-like growth factors in a class of generalized acquired lipoatrophic diabetes mellitus (Lawrencesyndrome) connected with autoantibodies against adipocyte membranes.
Exp Clin Endocrinol Diabetes, 106 (1998), pp. 79-84
[59.]
A. Simons.
Eine seltnen Trophoneurose: “Lipodistrophia progressiva”.
Z Ges Neurol Psychiat, 5 (1911), pp. 29-38
[60.]
W.T.C. Yuh, J.S. Collison, W.J. Sickels, T.J. Barloon, D.C. Brennan, M.J. Flanigan.
Partial lipodystrophy. Magnetic resonance findings in one case.
J Comput Tomogr, 12 (1988), pp. 287-291
[61.]
J.H. Peter, S. Gregoor, E.F.H. van Bommel, C. Ketterings, J.L.C.M. van Saase, P. Kramer.
Progressive lipodystrophy, a diagnosis at a glance.
Nephrol Dial Transplant, 13 (1998), pp. 507-509
[62.]
D. O'Mahony, S. O'Mahony, M.J. Whelton, J. McKiernan.
Partial lipodystrophy in coeliac disease.
Gut, 31 (1990), pp. 717-718
[63.]
J.C. Braimon, D.E. Moller.
Hereditary and acquired syndromes of severe insulin resistance.
Textbook of Diabetes, pp. 11-26
[64.]
A. Carr, K. Samaras, S. Burton, M. Law, J. Freund, D.J. Chisholm, et al.
A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance in patient receiving HIV protease inhibitors.
AIDS, 12 (1998), pp. F51-F58
[65.]
A. Carr, D.A. Cooper.
Adverse effects of antiretroviral therapy.
Lancet, 356 (2000), pp. 1423-1430
[66.]
C. Gervasoni, A.L. Ridolfo, G. Trifirò, S. Santambrogio, G. Norbiato, M. Musicco, et al.
Redistribution of body fat in HIV-infected women undergoing combined antiretroviral therapy.
AIDS, 13 (1999), pp. 465-472
[67.]
A. Carr, J. Miller, M. Law, D.A. Cooper.
A syndrome of lipoatrophy, lactic academia and liver dysfunction associated with HIV nucleoside analogue therapy: contribution to the protease inhibitor-related lipodystrophy.
AIDS, 14 (2000), pp. F25-F32
[68.]
M. Saves, F. Raffi, J. Capeau, W. Rozenbaum, J.M. Ragnaud, C. Perronne, et al.
Factors related to lipodystrophy and metabolic alterations in patients with human immunodeficiency virus infection receiving highly active antiretroviral therapy.
Clin Infect Dis, 15 (2002), pp. 1396-1405
[69.]
K. Brinkman, J.A. Smeitink, J.A. Rominjn, P. Reiss.
Mitochondrial toxicity induced by nucleoside-analogue reverse-transcriptase inhibitors is a key factor in the pathogenesis of antiretroviraltherapy-related lipodystrophy.
Lancet, 354 (1999), pp. 1112-1115
[70.]
J.P. Bastard, M. Caron, H. Vidal, V. Jan, M. Auclair, C. Vigouroux, et al.
Association between altered expression of adipogenic factor SREBP1 in lipoatrophic adipose tissue from HIV-1-infected patients and abnormal adipocyte differentiation and insulin resistance.
Lancet, 359 (2002), pp. 1026-1031
[71.]
C. Hadigan, K. Miller, C. Corcoran, E. Anderson, N. Basgoz, S. Grinspoon.
Fasting hyperinsulinemia and changes in regional body composition in human immunodeficiency virus-infected women.
J Clin Endocrinol Metab, 84 (1999), pp. 1932-1937
[72.]
E. Martínez, C. Fernández-Miranda, I. Conget, et al.
Actitud ante las alteraciones metabólicas y de distribución de la grasa corporal en pacientes infectados por el virus de la inmunodeficiencia humana que reciben tratamiento antirretroviral. Documento de consenso de Gesida y del Plan Nacional sobre el sida. Grupo de Estudio del sida.
Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica, (2002),
[73.]
E. Martinez, A. Mocroft, M.A. Garcia-Viejo, J.B. Perez-Cuevas, J.L. Blanco, J. Mallolas, et al.
Risk of lipodystrophy in HIV-1-infected patients treated with protease inhibitors: a prospective cohort study.
[74.]
R. Roche, I. Poizot-Martin, C.M. Yazidi, E. Compe, J.A. Gastaut, R. Torres Panells.
Effects of antiretroviral drugs combinations on the differentiation of adipocytes.
AIDS, 16 (2002), pp. 13-20
[75.]
S.A. Amiel.
Insulin injection treatment and its complications.
Textbook of diabetes, pp. 16-33
[76.]
E. Nagore, J.M. Sánchez-Motilla, M. Rodríguez-Serna, J.J. Vilata, A. Aliaga.
Lipoatrophia semicircularis – a traumatic panniculitis: report of seven cases and review of the literature.
J Am Acad Dermatol, 39 (1998), pp. 879-881
[77.]
A.C. De Groot.
Is lipoatrophia semicircularis induced by pressure?.
Br J Dermatol, 131 (1994), pp. 887-890
[78.]
L. Requena, E. Sánchez Yus.
Panniculitis Part II. Mostly lobular panniculitis.
J Am Acad Dermatol, 45 (2001), pp. 325-361
[79.]
S. Imamura, M. Yamada, K. Yamamoto, Y. Yamanishi.
Infantile centrifugal abdominal lipodystrophy.
Hautarzt, 30 (1979), pp. 360-364
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