Lipid homeostasis, lipotoxicity and the metabolic syndrome

Roger H Unger, Gregory O. Clark, Philipp E Scherer, Lelio Orci

Research output: Contribution to journalReview article

352 Scopus citations

Abstract

In the 20th century industrialized nations have become afflicted with an unprecedented pandemic of increased adiposity. In the United States, the epicenter of the epidemic, over 2/3 of the population, is overweight and 1 of every 6 Americans carries the diagnosis of metabolic syndrome. Although genes determine susceptibility to environmental factors, the epidemic is clearly due to increased consumption of calorie-dense, highly lipogenic foods, coupled with a marked decrease in physical exertion resulting from modern technologies. If this lifestyle continues, morbid consequences are virtually inevitable. They include type II diabetes and a cluster of disorders known as "the metabolic syndrome" usually appearing in middle age. The morbid consequences of the chronic caloric surplus are buffered before middle age by the partitioning of these calories as fat in the adipocyte compartment which is specifically designed to store triglycerides. Leptin has been proposed as the major hormonal regulator of the partitioning of surplus calories. However, multiple factors can determine the storage capacity of the fat tissue and when it is exceeded ectopic lipid deposition begins. The organs affected in metabolic syndrome include skeletal muscle, liver, heart and pancreas, which are now known to contain abnormal levels of triglycerides. While neutral fat is probably harmless, it is an index of ectopic lipid overload. Fatty acid derivatives can interfere with the function of the cell and ultimately lead to its demise through lipoapoptosis, the consequences of which are gradual organ failure.

Original languageEnglish (US)
Pages (from-to)209-214
Number of pages6
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1801
Issue number3
DOIs
StatePublished - Mar 1 2010

Keywords

  • Adipocyte
  • Apoptosis
  • Caloric surplus
  • Leptin
  • Lipotoxicity
  • Metabolic syndrome

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Lipid homeostasis, lipotoxicity and the metabolic syndrome'. Together they form a unique fingerprint.

  • Cite this