Longevity, lipotoxicity and leptin: The adipocyte defense against feasting and famine

Roger H Unger

Research output: Contribution to journalArticlepeer-review

124 Scopus citations


In this review, we propose that actions of the lipid-lowering, apoptosis-inhibiting effects of certain "longevity genes" oppose the life-shortening consequences of lipotoxicity and lipoapoptosis. We note that lipotoxicity occurs whenever leptin action is deficient, or whenever satiety is overridden, as in forced or voluntary overfeeding ("supersizing"). The role of hyperleptinemia, we suggest, is to extend survival during famine by permitting the storage of surplus calories in adipocytes without concomitant injury to nonadipose tissues from ectopic lipid deposits. It achieves this lipid partitioning by (1) restraining the level of overnutrition so as not to exceed the available adipocyte storage space and (2) enhancing oxidation of any ectopic lipid overflow: The mechanisms of lipoapoptosis are discussed, and the possibility that metabolic syndrome is the human equivalent of rodent lipotoxicity is suggested.

Original languageEnglish (US)
Pages (from-to)57-64
Number of pages8
Issue number1 SPEC. ISS.
StatePublished - Jan 2005


  • Apoptosis
  • Ceramide
  • Leptin
  • Lipodystrophy
  • Lipotoxicity
  • Longevity
  • Metabolic syndrome
  • Obesity

ASJC Scopus subject areas

  • Biochemistry


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