Lipodystrophies are inherited or acquired disorders characterized by selective, but variable, loss of adipose tissue. These patients are predisposed to developing insulin resistance and its complications such as premature diabetes mellitus, hypertriglyceridemia, low levels of high-density lipoprotein (HDL) cholesterol, and nonalcoholic hepatic steatosis. The severity of metabolic complications in general parallels the extent of body fat loss, and patients with generalized lipodystrophies have more severe metabolic derangements compared to those with partial lipodystrophies. Advances have been made in elucidating the molecular basis of many inherited lipodystrophies and defects in genes involved in adipocyte development, differentiation, and death pathways as well as in triglyceride biosynthesis and lipid droplet formation are implicated. On the other hand, acquired lipodystrophies are mainly due to the destruction of adipocytes due to autoimmune mechanisms, drugs, or other unknown factors. Many patients develop extreme hypertriglyceridemia and chylomicronemia predisposing them to acute pancreatitis and thus need to be differentiated from those with type 1 hyperlipoproteinemia. Others with accumulation of very low-density lipoproteins (VLDL) and remnant lipoproteins may be predisposed to develop coronary heart disease. Leptin replacement therapy has been recently approved by the US Food and Drug Administration for improving metabolic complications in patients with generalized lipodystrophies. Improvement of diabetes control, use of fibrates and fish oil, and avoidance of estrogen preparations in females are key strategies to improve dyslipidemias in patients with lipodystrophies.
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