Abstract
Lipodystrophy syndromes are rare diseases originating from a generalized or partial loss of adipose tissue. Adipose tissue dysfunction results from heterogeneous genetic or acquired causes, but leads to similar metabolic complications with insulin resistance, diabetes, hypertriglyceridemia, nonalcoholic fatty liver disease, dysfunctions of the gonadotropic axis and endocrine defects of adipose tissue with leptin and adiponectin deficiency. Diagnosis, based on clinical and metabolic investigations, and on genetic analyses, is of major importance to adapt medical care and genetic counseling. Molecular and cellular bases of these syndromes involve, among others, altered adipocyte differentiation, structure and/or regulation of the adipocyte lipid droplet, and/or premature cellular senescence. Lipodystrophy syndromes frequently present as systemic diseases with multi-tissue involvement. After an update on the main molecular bases and clinical forms of lipodystrophy, we will focus on topics that have recently emerged in the field. We will discuss the links between lipodystrophy and premature ageing and/or immuno-inflammatory aggressions of adipose tissue, as well as the relationships between lipomatosis and lipodystrophy. Finally, the indications of substitutive therapy with metreleptin, an analog of leptin, which is approved in Europe and USA, will be discussed.
Highlights
Lipodystrophy syndromes are rare diseases characterized by generalized or segmental lack of adipose tissue, and by insulin resistance-related metabolic complications such as diabetes, hypertriglyceridemia, hepatic steatosis, and ovarian hyperandrogenism in women
Upper-body fat overgrowth, LIPE: Hormone-sensitive-lipase, release of fatty acids lipoatrophy of limbs, insulin resistance-related from stored triglycerides in adipocytes and release of traits, muscular atrophy in some cases cholesterol from cholesterol esters in steroidogenic tissues
LMNA pathogenic variants cause several different laminopathies including muscular dystrophy, cardiomyopathy, neuropathy, lipodystrophy, and syndromes of accelerated aging. Both typical FPLD2/Dunnigan syndrome, characterized by partial lipodystrophy and insulin resistance-related complications, and the extremely severe Hutchinson-Gilford accelerated ageing syndrome with generalized lipoatrophy are due to LMNA variants
Summary
Lipodystrophy syndromes are rare diseases characterized by generalized or segmental lack of adipose tissue, and by insulin resistance-related metabolic complications such as diabetes, hypertriglyceridemia, hepatic steatosis, and ovarian hyperandrogenism in women. Beyond the diversity of clinical forms, lipodystrophy syndromes share adipose tissue dysfunction as a key pathophysiological feature, with gene pathogenic variants mostly affecting adipocyte development, differentiation and/or functions (Figure 1). Generalized or partial lipoatrophy is a clinical feature of several diseases with accelerated ageing called progeroid syndromes (Table 1).
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