Lipodystrophien

Zusammenfassung

Lipodystrophien sind sehr seltene Krankheiten, charakterisiert durch das FRehlen von Fettgbewebe. Der Verlust von Fettgewebe kann genetische oder immunologische Gründe haben, aber auch verursacht sein durch Infektionen oder Gabe bestimmter Medikamente. Das Ausmaß an metabolischen Komplikationen wie Insulinresistenz, Diabetes mellitus, Hypertriglyzeridämie und Fettleber steigt an mit Ausmaß des Fettverlusts.

Lipodystrophien können in zwei Gruppen unterteilt werden, die familiären und die erworbenen Formen. Sowohl für eine familiäre, als auch für eine erworbene Form konnten erst kürzlich ursächliche Mutationen gefunden werden. Im Moment helfen Mausmodelle, diese Syndrome besser verstehen zu lernen.

In dieser Übersichtsarbeit wird die neue Klassifizierung der Lipodystrophie-Syndrome vorgestellt, zudem werden aktuelle Forschungsergebnisse über die Pathogenese und Therapiemöglichkeiten zusammengefasst.

Abstract

The lipodystrophy syndromes are rare disorders characterized by the loss of adipose tissue. The loss of fat tissue can have genetic, immune, or infectious/drug-associated causes. With the extent of fat loss metabolic complications, such as insulin resistance, diabetes mellitus, hypertriglyceridemia, and fatty liver increase in severity. Lipodystrophies can be divided into two subtypes: familial and acquired. Causative mutations have recently been identified in one form of familial lipodystrophy as well as in one form of acquired lipodystrophy. Several mouse models might help understanding the development of these syndroms.

In this review article, the recently introduced classification of lipodystrophy syndromes is presented as well as new insights into pathogenesis and therapeutic strategies.

Schlüsselwörter

Lipodystrophie - Adipozyt - Fettzelldifferenzierung

Key words

Lipodystrophy - adipocyte - adipose differentiation

Literatur

• 1 Ailhaud G, Hauner H. Development of white adipose tissue. In: Bray G, Bouchard C, James WPT (Hrsg) Handbook of obesity, 359 - 378. Marcel Dekker New York; 1997
• 2 Arioglu E, Duncan-Morin J, Sebring N. , et al . Efficacy and safety of troglitazone in the treatment of lipodystrophy syndromes.  Ann Intern Med. 2000;  133(4) 263-274
• 3 Arioglu E, Simha V, Andewelt A. , et al .Treatment of patients with lipoatrophy: Efficacy of leptin treatment. Oral presentation, 1st International Workshop on Lipoatrophic Diabetes and other syndromes of lipodystrophy. NIH Bethesda, Maryland; 2001
• 4 Barraquer L. Histoire clinique d’un cas d’atrophie du tissu celluloadipeux.  Neurolog Zentralblatt. 1907;  26 1072
• 5 Berardinelli W. An undiagnosed endocrinometabolic syndrome: report of 2 cases.  J Clin Endocrinol. 1954;  14 193-204
• 6 Billings J K, Milgraum S S, Gupta A K. , et al . Lipoatrophic panniculitis: a possible autoimmune inflammatory disease of fat. Report of three cases.  Arch Dermatol. 1987;  123(12) 1662-1666
• 7 Chao L, Marcus-Samuels B, Mason M M,. et al . Adipose tissue is required for the antidiabetic, but not for the hypolipidemic, effect of thiazolidinediones.  J Clin Invest. 2000;  106(10) 1221-1228
• 8 Garg A. Lipodystrophies.  Am J Med. 2000;  108 143-152
• 9 Garg A, Wilson R, Barnes R. , et al . A gene for congentital generalized lipodytsrophy maps to human chromosome 9q34.  J Clin Endocrinol Metab. 1999;  84 3390-3394
• 10 Gavrilova O, Marcus-Samuels B, Graham D,. et al . Surgical implantation of adipose tissue reverses diabetes in lipoatrophic mice.  J Clin Inves. 2000;  105(3) 271-278
• 11 Gregoire F M, Smas C M, Sul H S. Understanding adipocyte differentiation.  Physiol Rev. 1998;  78(3) 783-809
• 12 Hauner H, Skurk T, Wabitsch M. Cultures of human adipose precursor cells.  Methods Mol Biol. 2001;  155 239-247
• 13 Hegele R A, Cao H, Anderson C M, Hramiak I M. Heterogeneity of nuclear lamin A mutations in Dunnigan-type familial partial lipodystrophy.  J Clin Endocrinol Metab. 2000;  85(9) 3431-3435
• 14 Hubler A, Abendroth K, Keiner T,. et al . Dysregulation of insulin-like growth factors in a case of generalized acquired lipoatrophic diabetes mellitus (Lawrence Syndrome) connected with autoantibodies against adipocyte membranes.  Exp Clin Endocrinol Diabetes. 1998;  106(1) 79-84
• 15 Madge S, Kinloch-de-Loes S,. et al . Lipodystrophy in patients naive to HIV protease inhibitors.  AIDS. 1999;  13(6) 735-737
• 16 Magré J, Delépine M, Khallouf E. , et al . Identification of the gene altered in Berardinelli Seip congenital lipodystrophy on chromosome 11q13.  Nature Medicine. 2001;  28 365-370
• 17 Mitchell S W. Singular absence of adipose matter in the upper half of the body.  Am J Med Sci. 1885;  90 105-106
• 18 Moitra J, Mason M M, Olive M,. et al . Life without white fat: a transgenic mouse.  Genes Dev. 1998;  12(20) 3168-3181
• 19 Peters J M, Barnes R, Bennett L,. et al . Localization of the gene for familial partial lipodystrophy (Dunnigan variety) to chromosome 1q21 - 22.  Nat Genet. 1998;  18(3) 292-295
• 20 Petersen K F, Arioglu E, Yu C. , et al .Effects of chronic leptin treatment on insulin action and liver and muscle triglyceride content in two patients with severe lipodystrophy. Poster presentation, 1st International Workshop on Lipoatrophic Diabetes and other syndromes of lipodystrophy. NIH Bethesda, Maryland; 2001
• 21 Reitman M L, Arioglu E, Gavrilova O, Taylor S I. Lipoatrophy revisited.  Trends Endocrinol Metab. 2000;  11(10) 410-416
• 22 Rosen E D, Spiegelman B M. Molecular regulation of adipogenesis.  Annu Rev Cell Dev Biol. 2000;  16 145-171
• 23 Seip M. Lipodystrophy and gigantism with associated endocrine manifestations: a new diencephalic syndrom?.  Acta Paediatrica. 1959;  48 555-574
• 24 Shackleton S, Lloyd D J, Jackson S N,. et al . LMNA, encoding lamin A/C, is mutated in partial lipodystrophy.  Nat Genet. 2000;  24(2) 153-156
• 25 Shimomura I, Hammer R E, Richardson J A. , et al . Insulin resistance and diabetes mellitus in transgenic mice expressing nuclear SREBP-1c in adipose tissue: model for congenital generalized lipodystrophy.  Genes Dev. 1998;  12(20) 3182-3194
• 26 Shimomura I, Hammer R E, Ikemoto S,. et al . Leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy.  Nature. 1999;  401(6748) 73-76
• 27 Silver K, Walston J, Plotnick L,. et al . Molecular scanning of beta-3-adrenergic receptor gene in total congenital lipoatrophic diabetes mellitus.  J Clin Endocrinol Metab. 1997;  82 3395-3398
• 28 Simons A. Eine seltene Trophoneurose: „Lipodystrophia progressiva”.  Z Ges Neurol Psychiat. 1911;  5 29-38
• 29 Vigouroux C, Khallouf E, Bourut C J,. et al . Genetic exclusion of 14 candidate genes in lipoatropic diabetes using linkage analysis in 10 consanguineous families.  J Clin Endocrinol Metab. 1997;  82 3438-3444
• 30 Vigouroux C, Fajas L, Khallouf E,. et al . Human peroxisome proliferator-activated receptor-gamma 2: genetic mapping, identification of a variant in the coding sequence, and exclusion as the gene responsible for lipoatrophic diabetes.  Diabetes. 1998;  47 490-492
• 31 Wabitsch M. The acquisition of obesity: insights from cellular and genetic research.  Proc Nutr Soc. 2000;  59 325-330
• 32 Wabitsch M, Brenner R E, Melzner I,. et al . Characterization of a human preadipocyte cell strain with high capacity for adipose differentiation.  Int J Obes Relat Metab Disord. 2001;  25(1) 8-15
• 33 Wentworth J M, Burris T P, Chatterjee V K. HIV protease inhibitors block human preadipocyte differentiation, but not via the PPARgamma/RXR heterodimer.  J Endocrinol. 2000;  164(2) R7-R10
• 34 Williams D G, Bartlett A, Duffus P. Identification of nephritic factor as an immunoglobulin.  Clin Exp Immunol. 1978;  33(3) 425-429
• 35 Zhang B, MacNaul K, Szalkowski D,. et al . Inhibition of adipocyte differentiation by HIV protease inhibitors.  J Clin Endocrinol Metab. 1999;  84(11) 4274-4277
• 36 Zuk P A, Zhu M, Mizuno H. , et al . Multilineage cells from human adipose tissue: implications for cell-based therapies.  Tissue Eng. 2001;  7(2) 211-228
• 37 1st International Workshop on Lipoatrophic Diabetes and other syndromes of lipodystrophy .NIH Bethesda, Maryland; 2001