Aging per se increases the susceptibility to free fatty acid-induced insulin resistance

Francine H. Einstein, Derek M. Huffman, Sigal Fishman, Elina Jerschow, Hye J. Heo, Gil Atzmon, Clyde Schechter, Nir Barzilai, Radhika H. Muzumdar

Research output: Contribution to journalArticlepeer-review

38 Scopus citations


Elevations in systemic free fatty acids (FFA) contribute to insulin resistance. To determine the effects of an acute elevation in FFA on insulin action with aging, we infused saline or intralipid (IL) during a hyperinsulinemic-euglycemic clamp in three groups of rats: young ad libitum-fed (YAL), old ad libitum-fed (OAL), and old on lifelong calorie restriction (OCR). The OCR group was included to distinguish between aging per se and age-related changes in body fat distribution. IL induced marked insulin resistance in both YAL and OCR, but the onset of insulin resistance was approximately two to three times more rapid in OCR as compared with YAL. In response to IL infusion, plasminogen-activating inhibitor-1 (PAI-1) expression was increased in subcutaneous fat from OAL animals. In visceral fat, a marked increase in PAI-1 and interleukin-6 expression was observed in OAL and OCR rats, but not YAL, in response to IL treatment. Thus, aging per se increases the inflammatory response to excess nutrients and vulnerability to FFA-induced insulin resistance with aging.

Original languageEnglish (US)
Pages (from-to)800-808
Number of pages9
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume65 A
Issue number8
StatePublished - Aug 2010


  • Adipokines
  • Aging
  • Calorie restriction
  • Insulin resistance
  • Lipids

ASJC Scopus subject areas

  • General Medicine


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