Congenital generalized lipodystrophies - New insights into metabolic dysfunction

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

Congenital generalized lipodystrophy (CGL) is a heterogeneous autosomal recessive disorder characterized by a near complete lack of adipose tissue from birth and, later in life, the development of metabolic complications, such as diabetes mellitus, hypertriglyceridaemia and hepatic steatosis. Four distinct subtypes of CGL exist: type 1 is associated with AGPAT2 mutations; type 2 is associated with BSCL2 mutations; type 3 is associated with CAV1 mutations; and type 4 is associated with PTRF mutations. The products of these genes have crucial roles in phospholipid and triglyceride synthesis, as well as in the formation of lipid droplets and caveolae within adipocytes. The predominant cause of metabolic complications in CGL is excess triglyceride accumulation in the liver and skeletal muscle owing to the inability to store triglycerides in adipose tissue. Profound hypoleptinaemia further exacerbates metabolic derangements by inducing a voracious appetite. Patients require psychological support, a low-fat diet, increased physical activity and cosmetic surgery. Aside from conventional therapy for hyperlipidaemia and diabetes mellitus, metreleptin replacement therapy can dramatically improve metabolic complications in patients with CGL. In this Review, we discuss the molecular genetic basis of CGL, the pathogenesis of the disease's metabolic complications and therapeutic options for patients with CGL.

Original languageEnglish (US)
Pages (from-to)522-534
Number of pages13
JournalNature Reviews Endocrinology
Volume11
Issue number9
DOIs
StatePublished - Sep 20 2015

Fingerprint

Congenital Generalized Lipodystrophy
Mutation
Triglycerides
Adipose Tissue
Diabetes Mellitus
Caveolae
Fat-Restricted Diet
Hypertriglyceridemia
Liver
Metabolic Diseases
Appetite
Plastic Surgery
Hyperlipidemias
Adipocytes
Molecular Biology
Phospholipids
Skeletal Muscle
Therapeutics
Parturition
Exercise

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Congenital generalized lipodystrophies - New insights into metabolic dysfunction. / Patni, Nivedita; Garg, Abhimanyu.

In: Nature Reviews Endocrinology, Vol. 11, No. 9, 20.09.2015, p. 522-534.

Research output: Contribution to journalArticle

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