R-α-lipoic acid does not reverse hepatic inflammation of aging, but lowers lipid anabolism, while accentuating circadian rhythm transcript profiles

Liam A. Finlay, Alex J. Michels, Judy A. Butler, Eric J. Smith, Jeffrey S. Monette, Regis F Moreau, Kate Petersen Shay, Balz Frei, Tory M. Hagen

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

To determine the effects of age and lipoic acid supplementation on hepatic gene expression, we fed young (3 mo) and old (24 mo) male Fischer 344 rats a diet with or without 0.2% (wt/wt) R-α-lipoic acid (LA) for 2 wk. Total RNA isolated from liver tissue was analyzed by Affymetrix microarray to examine changes in transcriptional profiles. Results showed elevated proinflammatory gene expression in the aging liver and evidence for increased immune cell activation and tissue remodeling, together representing 45% of the age-related transcriptome changes. In addition, age-related increases in transcripts of genes related to fatty acid, triglyceride, and cholesterol synthesis, including acetyl-CoA carbox-ylase-β (Acacb) and fatty acid synthase (Fasn), were observed. Supplementation of old animals with LA did not reverse the necroinflam-matory phenotype but, intriguingly, altered the expression of genes governing circadian rhythm. Most notably, Arntl, Npas2, and Per changed in a coordinated manner with respect to rhythmic transcription. LA further caused a decrease in transcripts of several bile acid and lipid synthesis genes, including Acacb and Fasn, which are regulated by first-order clock transcription factors. Similar effects of LA supplementation on bile acid and lipid synthesis genes were observed in young animals. Transcript changes of lipid metabolism genes were corroborated by a decrease in FASN and ACC protein levels. We conclude that advanced age is associated with a necroin-flammatory phenotype and increased lipid synthesis, while chronic LA supplementation influences hepatic genes associated with lipid and energy metabolism and circadian rhythm, regardless of age.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume302
Issue number5
DOIs
StatePublished - Mar 1 2012
Externally publishedYes

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Thioctic Acid
Circadian Rhythm
Inflammation
Lipids
Liver
Fatty Acid Synthases
Acetyl Coenzyme A
Genes
Bile Acids and Salts
Lipid Metabolism
Gene Expression
Phenotype
Inbred F344 Rats
Transcriptome
Energy Metabolism
Triglycerides
Transcription Factors
Fatty Acids
Cholesterol
RNA

Keywords

  • Circadian rhythm
  • Lipid metabolism
  • Microarray

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

R-α-lipoic acid does not reverse hepatic inflammation of aging, but lowers lipid anabolism, while accentuating circadian rhythm transcript profiles. / Finlay, Liam A.; Michels, Alex J.; Butler, Judy A.; Smith, Eric J.; Monette, Jeffrey S.; Moreau, Regis F; Shay, Kate Petersen; Frei, Balz; Hagen, Tory M.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 302, No. 5, 01.03.2012.

Research output: Contribution to journalArticle

Finlay, Liam A. ; Michels, Alex J. ; Butler, Judy A. ; Smith, Eric J. ; Monette, Jeffrey S. ; Moreau, Regis F ; Shay, Kate Petersen ; Frei, Balz ; Hagen, Tory M. / R-α-lipoic acid does not reverse hepatic inflammation of aging, but lowers lipid anabolism, while accentuating circadian rhythm transcript profiles. In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology. 2012 ; Vol. 302, No. 5.
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