Lipodystrophies-Disorders of the Fatty Tissue

Int J Mol Sci. 2020 Nov 20;21(22):8778. doi: 10.3390/ijms21228778.

Abstract

Lipodystrophies are a heterogeneous group of physiological changes characterized by a selective loss of fatty tissue. Here, no fat cells are present, either through lack of differentiation, loss of function or premature apoptosis. As a consequence, lipids can only be stored ectopically in non-adipocytes with the major health consequences as fatty liver and insulin resistance. This is a crucial difference to being slim where the fat cells are present and store lipids if needed. A simple clinical classification of lipodystrophies is based on congenital vs. acquired and generalized vs. partial disturbance of fat distribution. Complications in patients with lipodystrophy depend on the clinical manifestations. For example, in diabetes mellitus microangiopathic complications such as nephropathy, retinopathy and neuropathy may develop. In addition, due to ectopic lipid accumulation in the liver, fatty liver hepatitis may also develop, possibly with cirrhosis. The consequences of extreme hypertriglyceridemia are typically acute pancreatitis or eruptive xanthomas. The combination of severe hyperglycemia with dyslipidemia and signs of insulin resistance can lead to premature atherosclerosis with its associated complications of coronary heart disease, peripheral vascular disease and cerebrovascular changes. Overall, lipodystrophy is rare with an estimated incidence for congenital (<1/1.000.000) and acquired (1-9/100.000) forms. Due to the rarity of the syndrome and the phenotypic range of metabolic complications, only studies with limited patient numbers can be considered. Experimental animal models are therefore useful to understand the molecular mechanisms in lipodystrophy and to identify possible therapeutic approaches.

Keywords: acquired; generalized; genetics; lipodystrophy.

Publication types

  • Review

MeSH terms

  • Acyltransferases / deficiency
  • Acyltransferases / genetics
  • Adipose Tissue / metabolism
  • Adipose Tissue / pathology
  • Animals
  • Atherosclerosis / etiology
  • Atherosclerosis / genetics*
  • Atherosclerosis / metabolism
  • Atherosclerosis / pathology
  • Body Fat Distribution
  • Coronary Disease / etiology
  • Coronary Disease / genetics*
  • Coronary Disease / metabolism
  • Coronary Disease / pathology
  • Diabetes Mellitus / etiology
  • Diabetes Mellitus / genetics*
  • Diabetes Mellitus / metabolism
  • Diabetes Mellitus / pathology
  • Disease Models, Animal
  • Fatty Liver / complications
  • Fatty Liver / genetics*
  • Fatty Liver / metabolism
  • Fatty Liver / pathology
  • Humans
  • Hypertriglyceridemia / complications
  • Hypertriglyceridemia / genetics*
  • Hypertriglyceridemia / metabolism
  • Hypertriglyceridemia / pathology
  • Insulin Resistance
  • Lamin Type A / deficiency
  • Lamin Type A / genetics
  • Lipid Metabolism / genetics
  • Lipodystrophy / complications
  • Lipodystrophy / genetics*
  • Lipodystrophy / metabolism
  • Lipodystrophy / pathology
  • Pancreatitis / etiology
  • Pancreatitis / genetics
  • Pancreatitis / metabolism
  • Pancreatitis / pathology
  • Xanthomatosis / etiology
  • Xanthomatosis / genetics
  • Xanthomatosis / metabolism
  • Xanthomatosis / pathology

Substances

  • LMNA protein, human
  • Lamin Type A
  • Acyltransferases
  • 2-acylglycerophosphate acyltransferase