Plasma triglycerides are not related to tissue lipids and insulin sensitivity in elderly following PPAR-α agonist treatment

Melanie G. Cree, Bradley R. Newcomer, Laura K. Read, Melinda Sheffield-Moore, Douglas Paddon-Jones, David Chinkes, Asle Aarsland, Robert R. Wolfe

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Increases in plasma lipids, tissue triglycerides and decreases in mitochondrial function have been linked to insulin resistance and aging. In animals, peroxisome proliferator-activated receptor-α (PPAR-α) agonists decrease plasma lipids, intramyocellular fat (IMCL) and liver fat (LFAT) and improve mitochondrial β-oxidative function and insulin sensitivity, but the effects in elderly were not known. Insulin sensitivity was assessed with a 2-h oral glucose tolerance test, magnetic resonance spectroscopy was used to asses IMCL, LFAT and plasma lipids were measured before and after 6, 11 and 61 days of PPAR-α agonist (fenofibrate) administration in 19 elderly (age 70 ± 1 years) volunteers. Volunteers were stratified into healthy (N = 7) and insulin resistant (N = 12) groups. The baseline insulin sensitivity index (8.1 ± 1.2 vs. 3.8 ± 0.5, healthy vs. insulin resistant; P < 0.001) was significantly higher in the healthy group. Fenofibrate treatment induced significant reductions in plasma triglycerides (P < 0.001) and total cholesterol (P < 0.001) in both groups. Nonetheless, neither fasted free fatty acids, glucose, insulin, nor insulin sensitivity improved in either group (day 1 vs. day 61, 8.1 ± 1.2 vs. 8.1 ± 0.9, healthy; and 3.8 ± 0.5 vs. 4.2 ± 0.05, insulin resistant). Furthermore, there was no change in IMCL or LFAT. These results indicate that whereas fenofibrate significantly lowers plasma lipids it neither affects insulin sensitivity nor intracellular lipids in elderly.

Original languageEnglish
Pages (from-to)558-565
Number of pages8
JournalMechanisms of Ageing and Development
Volume128
Issue number10
DOIs
StatePublished - Oct 2007

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Keywords

  • Aging
  • Insulin resistance
  • Intramuscular triglyceride
  • Liver fat
  • Plasma lipids

ASJC Scopus subject areas

  • Aging
  • Biochemistry
  • Developmental Biology
  • Developmental Neuroscience

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