Inserm U859, service d'endocrinologie et maladies métaboliques, hôpital Huriez, CHRU de Lille, 1, rue Polonovski, 59000 Lille, France.
Ann Endocrinol (Paris). 2012 Jun;73(3):170-89. doi: 10.1016/j.ando.2012.04.010. Epub 2012 Jun 28.
The spectrum of adipose tissue diseases ranges from obesity to lipodystrophy, and is accompanied by insulin resistance syndrome, which promotes the occurrence of type 2 diabetes, dyslipidemia and cardiovascular complications. Lipodystrophy refers to a group of rare diseases characterized by the generalized or partial absence of adipose tissue, and occurs with or without hypertrophy of adipose tissue in other sites. They are classified as being familial or acquired, and generalized or partial. The genetically determined partial forms usually occur as Dunnigan syndrome, which is a type of laminopathy that can also manifest as muscle, cardiac, neuropathic or progeroid involvement. Gene mutations encoding for PPAR-gamma, Akt2, CIDEC, perilipin and the ZMPSTE 24 enzyme are much more rare. The genetically determined generalized forms are also very rare and are linked to mutations of seipin AGPAT2, FBN1, which is accompanied by Marfan syndrome, or of BANF1, which is characterized by a progeroid syndrome without insulin resistance and with early bone complications. Glycosylation disorders are sometimes involved. Some genetically determined forms have recently been found to be due to autoinflammatory syndromes linked to a proteasome anomaly (PSMB8). They result in a lipodystrophy syndrome that occurs secondarily with fever, dermatosis and panniculitis. Then there are forms that are considered to be acquired. They may be iatrogenic (protease inhibitors in HIV patients, glucocorticosteroids, insulin, graft-versus-host disease, etc.), related to an immune system disease (sequelae of dermatopolymyositis, autoimmune polyendocrine syndromes, particularly associated with type 1 diabetes, Barraquer-Simons and Lawrence syndromes), which are promoted by anomalies of the complement system. Finally, lipomatosis is currently classified as a painful form (adiposis dolorosa or Dercum's disease) or benign symmetric multiple form, also known as Launois-Bensaude syndrome or Madelung's disease, which are sometimes related to mitochondrial DNA mutations, but are usually promoted by alcohol. In addition to the medical management of metabolic syndrome and the sometimes surgical treatment of lipodystrophy, recombinant leptin provides hope for genetically determined lipodystrophy syndromes, whereas modifications in antiretroviral treatment and tesamorelin, a GHRH analog, is effective in the metabolic syndrome of HIV patients. Other therapeutic options will undoubtedly be developed, dependent on pathophysiological advances, which today tend to classify genetically determined lipodystrophy as being related to laminopathy or to lipid droplet disorders.
脂肪组织疾病的范围从肥胖到脂肪营养不良，伴随着胰岛素抵抗综合征，这会促进 2 型糖尿病、血脂异常和心血管并发症的发生。脂肪营养不良是一组罕见的疾病，其特征为全身性或局部脂肪组织缺失，并伴有或不伴有其他部位脂肪组织的肥大。它们分为家族性或获得性、全身性或局部性。遗传性部分形式通常表现为 Dunnigan 综合征，这是一种层粘连蛋白病，也可表现为肌肉、心脏、神经病或早老性病变。编码 PPAR-γ、Akt2、CIDEC、 perilipin 和 ZMPSTE24 酶的基因突变则更为罕见。遗传性全身性形式也非常罕见，与 seipin AGPAT2、FBN1 的基因突变有关，FBN1 基因突变伴有马凡综合征，或 BANF1 的基因突变，其特征为早老性综合征而无胰岛素抵抗，且伴有早期骨并发症。糖基化疾病有时也会涉及。最近发现一些遗传性形式是由于与蛋白酶体异常相关的自身炎症综合征引起的（PSMB8）。它们导致脂肪营养不良综合征，该综合征继发于发热、皮肤病和脂膜炎。然后是一些被认为是获得性的形式。它们可能是医源性的（HIV 患者的蛋白酶抑制剂、糖皮质激素、胰岛素、移植物抗宿主病等），与免疫系统疾病有关（皮肌炎后遗症、自身免疫性多内分泌综合征，特别是与 1 型糖尿病、Barraquer-Simons 和 Lawrence 综合征相关），这些疾病是由补体系统异常引起的。最后，脂肪增多症目前被归类为疼痛形式（脂肪痛或 Dercum 病）或良性对称多发性形式，也称为 Launois-Bensaude 综合征或 Madelung 病，这些疾病有时与线粒体 DNA 突变有关，但通常是由酒精引起的。除了代谢综合征的医学管理和脂肪营养不良的有时手术治疗外，重组瘦素为遗传性脂肪营养不良综合征带来了希望，而抗逆转录病毒治疗的改变和 GHRH 类似物 tesamorelin 对 HIV 患者的代谢综合征有效。其他治疗选择无疑将得到发展，这取决于病理生理学的进展，目前倾向于将遗传性脂肪营养不良归类为与层粘连蛋白病或脂滴疾病有关。
