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Gene expression-based comparison of PQQ and known transcriptional regulators

ABSTRACT: Pyrroloquinoline quinone (PQQ) is a naturally occurring compound and known to improve growth and reproductive performance when added to diets of PQQ-deprived rodents. To understand its mechanism action, changes in hepatic gene expression were measured in rats fed diets with or without added PQQ. Gene expression changes for PQQ supplemented (EC50 ~ 3 nmol PQQ/Kg diet) or deficient rats were assayed by expression microarray analysis and compared to those for known transcriptional regulators (epicatechin; Epi; dexamethasone, Dex; clofibrate, Clo; phenobarbital, Pb). Two principal expression clusters were observed; one for Dex and another for Pb, Epi, Clo, and PQQ. Within the latter, a PQQ subcluster containing a unique group of genes for cell signaling and transport functions. Next, short and long term PQQ depletion and repletion protocols (48 or 36 h, respectively) were performed, leading to changes in hepatic gene expression for both time periods. Of the ~10,000 genes and ESTs analyzed, 4.7% of the transcripts were sensitive to changes in PQQ dietary status. PQQ deprivation generally caused down regulation of genes associated with mitochondriogenesis, cell differentiation, and immune function. These gene expression changes provide the basis for most of the previously published functional observations associated with PQQ deficiency and PQQ administered in pharmacological amounts. To assess PQQ’s potential functions, we used gene expression profiling through microarray technology as part of a comprehensive approach to identify potential pathways and mechanisms. Given that the systemic effects of PQQ deprivation are influenced at levels of dietary intake in the micromolar range, highly purified diets were used to reduce expression from other bioactive factors and xenobiotics, such as those found in typical rodent chow diets. To establish if the changes in gene expression in response to PQQ exposure will follow a similar pattern as other xenobiotics, the responses to PQQ exposure were contrasted with those from exposure to epicatechin (Epi), dexamethasone (Dex), clofibrate (Clo), or phenobarbital (Pb). Dietary conditions were also chosen to clarify the response to short- and longer-term PQQ deprivation. A goal was to determine if specific changes in dietary protocol or patterns could be used to identify genes important to the function of PQQ. Because it has been observed that mitochondrial-related functions are influenced by PQQ, we hypothesized that changes in genes important to fatty acid and amino acid metabolism and mitochondrial function would be likewise affected by dietary levels of PQQ. The overall study was carried out using two experiments. In this specific experiment, the gene expression profiles of Sprague Dawley (SD) rats treated with different xenobiotics were compared to the gene expression profile of PQQ treated SD rats.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE16240 | GEO | 2009/08/01

SECONDARY ACCESSION(S): PRJNA115125

REPOSITORIES: GEO

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Project description:High-protein diets are known to reduce adiposity in the context of high carbohydrate and Western diets. However, few studies have investigated the specific high-protein effect on lipogenesis induced by a high-sucrose (HS) diet or fat deposition induced by high-fat feeding. We aimed to determine the effects of high protein intake on the development of fat deposition and partitioning in response to high-fat and/or HS feeding. A total of thirty adult male Wistar rats were assigned to one of the six dietary regimens with low and high protein, sucrose and fat contents for 5 weeks. Body weight (BW) and food intake were measured weekly. Oral glucose tolerance tests and meal tolerance tests were performed after 4th and 5th weeks of the regimen, respectively. At the end of the study, the rats were killed 2 h after ingestion of a calibrated meal. Blood, tissues and organs were collected for analysis of circulating metabolites and hormones, body composition and mRNA expression in the liver and adipose tissues. No changes were observed in cumulative energy intake and BW gain after 5 weeks of dietary treatment. However, high-protein diets reduced by 20 % the adiposity gain induced by HS and high-sucrose high-fat (HS-HF) diets. Gene expression and transcriptomic analysis suggested that high protein intake reduced liver capacity for lipogenesis by reducing mRNA expressions of fatty acid synthase (fasn), acetyl-CoA carboxylase a and b (Acaca and Acacb) and sterol regulatory element binding transcription factor 1c (Srebf-1c). Moreover, ketogenesis, as indicated by plasma β-hydroxybutyrate levels, was higher in HS-HF-fed mice that were also fed high protein levels. Taken together, these results suggest that high-protein diets may reduce adiposity by inhibiting lipogenesis and stimulating ketogenesis in the liver. Adult male Wistar rats were fed diets with varying amounts of protein, carbohydrates and fat for 5 weeks. At the end of the experiment, rats were killed and tanscriptome analysis was performed on pooled liver samples.

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Gene expression-based comparison of PQQ and known transcriptional regulators

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