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Biochem Biophys Res Commun. 2014 Jul 18;450(1):324-9. doi: 10.1016/j.bbrc.2014.05.112. Epub 2014 Jun 2.

Lipoic acid entrains the hepatic circadian clock and lipid metabolic proteins that have been desynchronized with advanced age.

Author information

1
Linus Pauling Institute, Oregon State University, United States.
2
Linus Pauling Institute, Oregon State University, United States; Biochemistry Biophysics Department, Oregon State University, United States.
3
Linus Pauling Institute, Oregon State University, United States; Biochemistry Biophysics Department, Oregon State University, United States. Electronic address: Tory.Hagen@oregonstate.edu.

Abstract

It is well established that lipid metabolism is controlled, in part, by circadian clocks. However, circadian clocks lose temporal precision with age and correlates with elevated incidence in dyslipidemia and metabolic syndrome in older adults. Because our lab has shown that lipoic acid (LA) improves lipid homeostasis in aged animals, we hypothesized that LA affects the circadian clock to achieve these results. We fed 24 month old male F344 rats a diet supplemented with 0.2% (w/w) LA for 2 weeks prior to sacrifice and quantified hepatic circadian clock protein levels and clock-controlled lipid metabolic enzymes. LA treatment caused a significant phase-shift in the expression patterns of the circadian clock proteins Period (Per) 2, Brain and Muscle Arnt-Like1 (BMAL1), and Reverse Erythroblastosis virus (Rev-erb) β without altering the amplitude of protein levels during the light phase of the day. LA also significantly altered the oscillatory patterns of clock-controlled proteins associated with lipid metabolism. The level of peroxisome proliferator-activated receptor (PPAR) α was significantly increased and acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) were both significantly reduced, suggesting that the LA-supplemented aged animals are in a catabolic state. We conclude that LA remediates some of the dyslipidemic processes associated with advanced age, and this mechanism may be at least partially through entrainment of circadian clocks.

KEYWORDS:

Aging; Circadian; Corticosterone; Dyslipidemia; Entrainment; Peroxisome proliferator-activated receptor

PMID:
24944020
PMCID:
PMC4147855
DOI:
10.1016/j.bbrc.2014.05.112
[Indexed for MEDLINE]
Free PMC Article

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