Monogenic disorders of obesity and body fat distribution

Dali Chen, Abhimanyu Garg

Research output: Contribution to journalReview articlepeer-review

43 Scopus citations


Recently, great progress has been made towards understanding the molecular basis of body fat regulation. Identification of mutations in several genes in spontaneous monogenic animal models of obesity and development of transgenic models have indicated the physiological roles of many genes in the regulation of body fat distribution. In humans, mutations in leptin, leptin receptor, prohormone convertase 1 (PC1), pro- opiomelanocortin (POMC), melanocortin 4-receptor (MC4-R), and peroxisome proliferator-activated receptor (PPAR) γ2 genes have been described in patients with severe obesity. Most of these obesity disorders exhibit a distinct phenotype with varying degrees of hypothalamic and pituitary dysfunction and a recessive inheritance, whereas MC4-R mutation has a nonsyndromic phenotype with dominant inheritance. These mutations suggest the critical role of central signaling systems composed of leptin/leptin receptor and α-melanocyte stimulating hormone/MC4-R in human energy homeostasis. Although the genetic basis of monogenic disorders of body fat distribution, such as congenital generalized lipodystrophy and familial partial lipodystrophy, Dunnigan variety, is still unknown, the genes for these have recently been localized to chromosomes 9q34 and 1q21-22, respectively. The advances in our knowledge of the phenotypic manifestations and underlying molecular mechanisms of genetic body fat disorders may lead to better treatment and prevention of obesity and other disorders of adipose tissue in the future.

Original languageEnglish (US)
Pages (from-to)1735-1746
Number of pages12
JournalJournal of lipid research
Issue number10
StatePublished - Oct 1999


  • Congenital generalized lipodystrophy
  • Familial partial lipodystrophy
  • Leptin
  • Leptin receptor
  • Melanocortin receptors
  • Melanocyte-stimulating hormone

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology


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