Elsevier

The Journal of Nutrition

Volume 143, Issue 8, August 2013, Pages 1211-1218
The Journal of Nutrition

Hepatic Amino Acid-Degrading Enzyme Expression Is Downregulated by Natural and Synthetic Ligands of PPARα in Rats1, 2, 3

https://doi.org/10.3945/jn.113.176354Get rights and content
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Abstract

Body nitrogen retention is dependent on the amount of dietary protein consumed, as well as the fat and carbohydrate content in the diet, due to the modulation of amino acid oxidation. PPARα is a transcription factor involved in the upregulation of the expression of enzymes of fatty acid oxidation. However, the role of putative PPARα response elements (PPREs) in the promoter of several amino acid-degrading enzymes (AADEs) is not known. The aim of this work was to study the effect of the synthetic ligand Wy 14643 and the natural ligands palmitate, oleate, and linoleate in rats fed graded concentrations of dietary protein (6, 20, or 50 g/100 g of total diet) on the expression of the AADEs histidase, serine dehydratase, and tyrosine aminotransferase. Thus, we fed male Wistar rats diets containing 6, 20, or 50% casein for 10 d. The results showed that addition of Wy 14643 to the diet significantly reduced the expression of the AADEs. Furthermore, the incubation of hepatocytes with natural ligands of PPARα or feeding rats with diets containing soybean oil, safflower oil, lard, or coconut oil as sources of dietary fat significantly repressed the expression of the AADEs. Gene reporter assays and mobility shift assays demonstrated that the PPRE located at −482 bp of the histidase gene actively bound PPARα in rat hepatocytes. These data indicate that PPARα ligands may reduce amino acid catabolism in rats.

Abbreviations

AADE
amino acid-degrading enzyme
AP
activator protein
CPT-1
carnitine palmitoyltransferase-1
HAL
histidine ammonia lyase
PKA
protein kinase A
PKC
protein kinase C
PPRE, PPAR
responsive element
RXR
retinoid X receptor
SDH
serine dehydratase
TAT
tyrosine aminotransferase
6-C
control rats fed 6% casein diet
6-Wy
rats fed 6% casein diet with 0.1% Wy 14643
20-C
control rats fed 20% casein diet
20-Wy
rats fed 20% casein diet with 0.1% Wy 14643
50-C
control rats fed 50% casein diet
50-Wy
rats fed 50% casein diet with 0.1% Wy 14643

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1

Supported by Consejo Nacional de Ciencia y Tecnologia, México grant no. 41799-M.

2

Author disclosures: G. Alemán, V. Ortiz, A. V. Contreras, G. Quiroz, G. Ordaz-Nava, E. Langley, N. Torres, and A. R. Tovar, no conflicts of interest.

3

Supplemental Table 1 and Figure 1 are available from the “Online Supporting Material” link in the online posting of the article and from the same link in the online table of contents at http://jn.nutrition.org.