Regulation of fatty acid homeostasis in cells

Novel role of leptin

Roger H Unger, Yan Ting Zhou, Lelio Orci

Research output: Contribution to journalArticle

348 Citations (Scopus)

Abstract

It is proposed that an important function of leptin is to confine the storage of triglycerides (TG) to the adipocytes, while limiting TG storage in nonadipocytes, thus protecting them from lipotoxicity. The fact that TG content in nonadipocytes normally remains within a narrow range, while that of adipocytes varies enormously with food intake, is consistent with a system of TG homeostasis in normal nonadipocytes. The facts that when leptin receptors are dysfunctional, TG content in nonadipocytes such as islets can increase 100-fold, and that constitutively expressed ectopic hyperleptinemia depletes TG, suggest that leptin controls the homeostatic system for intracellular TG. The fact that the function and viability of nonadipocytes is compromised when their TG content rises above or falls below the normal range suggests that normal homeostasis of their intracellular TG is critical for optimal function and to prevent lipoapoptosis. Thus far, lipotoxic diabetes of fa/fa Zucker diabetic fatty rats is the only proven lipodegenerative disease, but the possibility of lipotoxic disease of skeletal and/or cardiac muscle may require investigation, as does the possible influence of the intracellular TG content on autoimmune and neoplastic processes.

Original languageEnglish (US)
Pages (from-to)2327-2332
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number5
DOIs
StatePublished - Mar 2 1999

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Leptin
Triglycerides
Homeostasis
Fatty Acids
Adipocytes
Neoplastic Processes
Leptin Receptors
Myocardium
Reference Values
Skeletal Muscle
Eating

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Regulation of fatty acid homeostasis in cells : Novel role of leptin. / Unger, Roger H; Zhou, Yan Ting; Orci, Lelio.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 96, No. 5, 02.03.1999, p. 2327-2332.

Research output: Contribution to journalArticle

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