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Abstract
BackgroundPeroxisome proliferator-activated receptor-γ co-activator-1α (PGC-1α) is a member of the transcriptional coactivator family that plays a central role in the regulation of cellular energy metabolism under various physiological stimuli. During fasting, PGC-1α is induced in the liver and together with estrogen-related receptor a and γ (ERRαand ERRγ, orphan nuclear receptors with no known endogenous ligand, regulate sets of genes that participate in the energy balance program. We found that PGC-1α, ERRα and ERRγ was highly expressed in human kidney HK2 cells and that PGC-1α induced dynamic protein interactions on the ERRα chromatin. However, the effect of fasting on the expression of endogenous PGC-1α, ERRα and ERRγ in the kidney is not known.Methodology/Principal FindingsIn this study, we demonstrated by qPCR that the expression of PGC-1α, ERRα and ERRγ was increased in the mouse kidney after fasting. By using immunohistochemistry (IHC), we showed these three proteins are co-localized in the outer stripe of the outer medulla (OSOM) of the mouse kidney. We were able to collect this region from the kidney using the Laser Capture Microdissection (LCM) technique. The qPCR data showed significant increase of PGC-1α, ERRα and ERRγ mRNA in the LCM samples after fasting for 24 hours. Furthermore, the known ERRα target genes, mitochondrial oxidative phosphorylation gene COX8H and the tricarboxylic acid (TCA) cycle gene IDH3A also showed an increase. Taken together, our data suggest that fasting activates the energy balance program in the OSOM of the kidney.
Highlights
Nutrient balance and metabolic homeostasis in mammals are maintained by an intricate regulatory circuitry which is controlled by transcriptional mechanisms
While examining the kidney sections from the fasting animals, we noticed that the immunostaining of ERRa in the nuclei of proximal convoluted tubule (PCT) in the OSOM
Fasting induces the expression of coactivator PGC-1a and orphan nuclear receptor ERRa and ERRc in mouse kidney
Summary
Nutrient balance and metabolic homeostasis in mammals are maintained by an intricate regulatory circuitry which is controlled by transcriptional mechanisms. A primary fuel source shift from carbohydrate to ketone bodies occurres in the liver and kidney. This change is accompanied by increase of gluconeogenesis and fatty acid oxidation [1,2,3]. The kidney contains genes regulated by circadian rhythm whose relative expression levels are significantly affected by time of day and the feeding status. Their expression level could be further modified by fasting [9,10]. The effect of fasting on the expression of endogenous PGC1a, ERRa and ERRc in the kidney is not known
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