脂肪营养不良综合征

Lipodystrophic syndromes

脂肪营养不良综合征(lipodystrophic syndromes)是以皮下脂肪组织缺乏或萎缩为特征性表现的一组疾病的总称,脂肪萎缩可以是先天性的,也可以是获得性的,可以是全身性的,也可以是部分性的,部分性脂肪萎缩往往合并非萎缩部位脂肪组织的异常增生或堆积。临床上脂肪营养不良患者往往会合并多种的代谢紊乱如:重度胰岛素抵抗、糖耐量受损、糖尿病、血脂代谢紊乱、脂肪肝、基础代谢率增高、血清瘦素、脂联素水平下降等,表明脂肪组织对人体内分泌代谢系统起重要作用,故目前多数学者认为脂肪组织是人体最重要的内分泌器官之一,不仅脂肪细胞数量的改变可以影响内分泌代谢系统的平衡,而且脂肪细胞分布的异常也会导致多种代谢紊乱的发生。现代生物化学及分子遗传学的发展使我们越来越多的认识到脂肪营养不良的发病机制及生化特征,为其治疗提供了更多的选择,如瘦素、脂联素的替代治疗,过氧化物酶体增殖物活化受体(peroxisome proliferator-activated receptor gamma,PPAR-γ)激动剂(脂肪细胞分化过程中关键的转录激活因子)的应用都取得了良好的临床疗效,临床试验还证实应用生长激素(growth hormone,GH)及促生长激素释放激素(GH-releasing factors,GHRH)类似物也对脂肪萎缩及其分布异常有明显疗效,一系列的基础研究及临床试验使脂肪营养不良这个难治性疾病的治疗取得了革命性的进展。

The lipodystrophic syndromes are a heterogeneous group of congenital or acquired disorders characterized by either complete or partial lack of adipose tissue , which may occur in conjunction with pathological accumulation of fat in other distinct regions of the body. Patients with lipodystrophy suffer from numerous metabolic complications, such as severe insulin resistance, impaired glucose tolerance, diabetes mellitus, severe hyperlipidemia, progressive liver disease, and increased metabolic rate, serum leptin concentration can be low, indicating the importance of adipose tissue as an active endocrine organ. Not only does the total amount but also the appropriate distribution of fat deposits contribute to the metabolic state. Recent genetic and molecular research has improved our understanding of the mechanisms underlying lipodystrophy. Circulating levels of hormones secreted by adipose tissue, such as leptin and adiponectin, are greatly reduced in distinct subsets of patients with lipodystrophy, rationalizing the use of such hormones or agents that increase their circulating levels, such as peroxisome proliferator-activated receptor gamma（PPAR＇,/） agonists, in a subset of patients with lipodystrophy. Other novel therapeutic approaches, including the use of growth hormone （GH） and GH-releasing factors, are also being studied as potential additions to the therapeutic armamentarium. Insights from recent research efforts and clinical trials could potentially revolutionize the treatment of this difficult-to-treat condition.