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Lipodystrophy: metabolic insights from a rare disorder Huang-Doran I; Sleigh A; Rochford JJ; O'Rahilly S; Savage DBJ Endocrinol 2010[Dec]; 207 (3): 245-55Obesity, 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.|Adipose Tissue/metabolism[MESH]|Animals[MESH]|Dyslipidemias/genetics/*metabolism[MESH]|Fatty Liver/genetics/metabolism[MESH]|Female[MESH]|Gene Expression/genetics/physiology[MESH]|Humans[MESH]|Hyperandrogenism/genetics/metabolism[MESH]|Insulin Resistance/genetics/physiology[MESH]|Lipodystrophy/genetics/*metabolism/pathology[MESH]|Male[MESH]|Metabolic Syndrome/genetics/metabolism/pathology[MESH]|Mice[MESH]|Obesity/genetics/*metabolism[MESH] |
