Adipocyte differentiation impairment as well as lipid metabolism and transport problems – major causes of genetic lipodystrophies

Abstract

Lipodystrophies are heterogenic group of adipose tissue disorders with its general or partial atrophy. In case of congenital lipodystrophies disturbances of adipogenesis or/and alterations of adipocyte differentiation often occur leading to thermogenic adipocytes formation. Basic adipocyte functions can be perturbed, including improper synthesis of triacylglycerols and phospholipids of lipid droplet, but also impaired fatty acids release and intracellular lipid traffic. Lipodystrophy can result from weakening of adipose tissue structure, but also from improper function of both cytoskeleton and nuclear lamina leading to cell dysfunction. Lack of adipose tissue leads to a) increased plasma triacylglycerols level and ectopic fat accumulation in other tissues; b) total plasma cholesterol increase; c) plasma HDL-cholesterol decrease. Ectopic fat accumulation in liver can cause fatty liver and with time can lead to hepatomegaly and liver cirrhosis. Dysfunctions are proportional to the extent of fat tissue loss with generalized lipodystrophies patients developing complications at early ages. Diabetes and insulin resistance are common comorbidities. Improvement of diagnostic methods of medical genetics allows precise determination of their genotypes and correct diagnosis of patients suffering from lipodystrophy. For that reason number of described cases increased in recent years, also in Poland. New lipodystrophy types were described. Therefore there is a need to bring lipodystrophy syndromes for the attention of primary care physicians, pediatricians and endocrinologists.