Beyond lipids, pharmacological PPARα activation has important effects on amino acid metabolism as studied in the rat

Sheikh, Kashif; Camejo, Germán; Lanne, Boel; Halvarsson, Torbjörn; Landergren, Marie; Oakes, Nicholas D.

doi:10.1152/ajpendo.00254.2006

Cited by 46 publications

(65 citation statements)

References 40 publications

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“…The amino acids linked to the urea cycle, which include aspartate, arginine, and citrulline, are increased in PPAR-a knockout mice compared with wild-type mice (59). In a model of dyslipidemia and insulin resistance, however, the PPAR-a agonist Wy14643 produces significant alterations in the plasma levels of both amino acids and nitrogen-containing metabolites, suggesting important effects on amino acid mobilization and catabolism (60).…”

Section: Metabolic Functions Of Ppar-amentioning

confidence: 99%

PPAR-α as a Key Nutritional and Environmental Sensor for Metabolic Adaptation

Contreras¹,

Torres²,

Tovar³

2013

Advances in Nutrition

194

148

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Peroxisome proliferator-activated receptors (PPARs) are transcription factors that belong to the superfamily of nuclear hormone receptors and regulate the expression of several genes involved in metabolic processes that are potentially linked to the development of some diseases such as hyperlipidemia, diabetes, and obesity. One type of PPAR, PPAR-α, is a transcription factor that regulates the metabolism of lipids, carbohydrates, and amino acids and is activated by ligands such as polyunsaturated fatty acids and drugs used to treat dyslipidemias. There is evidence that genetic variants within the PPARα gene have been associated with a risk of the development of dyslipidemia and cardiovascular disease by influencing fasting and postprandial lipid concentrations; the gene variants have also been associated with an acceleration of the progression of type 2 diabetes. The interactions between genetic PPARα variants and the response to dietary factors will help to identify individuals or populations who can benefit from specific dietary recommendations. Interestingly, certain nutritional conditions, such as the prolonged consumption of a protein-restricted diet, can produce long-lasting effects on PPARα gene expression through modifications in the methylation of a specific locus surrounding the PPARα gene. Thus, this review underlines our current knowledge about the important role of PPAR-α as a mediator of the metabolic response to nutritional and environmental factors.

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Section: Metabolic Functions Of Ppar-amentioning

confidence: 99%

PPAR-α as a Key Nutritional and Environmental Sensor for Metabolic Adaptation

Contreras¹,

Torres²,

Tovar³

2013

Advances in Nutrition

194

148

View full text Add to dashboard Cite

show abstract

“…Furthermore, it has been suggested that treatment with synthetic ligands of PPARa is able to decrease the mRNA concentration of several enzymes responsible for amino acid catabolism and the urea cycle (20,21). Recently, it was also suggested that PPARa deficiency affects arginine metabolism, impairing NO synthesis (22).…”

Section: Introductionmentioning

confidence: 99%

Hepatic Amino Acid-Degrading Enzyme Expression Is Downregulated by Natural and Synthetic Ligands of PPARα in Rats

Alemán

Ortíz

Contreras

et al. 2013

The Journal of Nutrition

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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.

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“…9 Data in literature show that administration of PPARα agonist in mice results in increased levels and rate of turnover of glycine and serine in the plasma. 35 The physiological significance of changes in glycine and serine metabolism during protein restriction, other than as source of methyl groups, has not been determined. It has been postulated that restriction of dietary protein results in higher methylation demand and a high rate transmethylation and consequently high rate of synthesis of serine and glycine.…”

Section: Discussionmentioning

confidence: 99%

Effect of multi-nutrient insufficiency on markers of one carbon metabolism in young women: response to a methionine load

et al. 2015

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Background Multinutrient insufficiencies as a consequence of nutritional and economic factors are common in India and other developing countries. We have examined the impact of multi-nutrient insufficiency on markers of one carbon metabolism in the blood, and response to a methionine load in clinically healthy young women. Design & Methods Young women from Pune, India (n=10) and Cleveland, USA (n=13) were studied. Blood samples were obtained in the basal state and following an oral methionine load (50mg/kg of body weight in orange juice). Plasma concentrations of vitamin B12, folate and B6 were measured in the basal state. The effect of methionine load on the levels of methionine, total homocysteine, cysteine, glutathione and amino acids was examined. Results Indian women were significantly shorter and lighter compared with the American women and had lower plasma concentration of vitamins B12, folate and B6, essential amino acids and glutathione, but higher concentration of total homocysteine. The homocysteine response to methionine load was higher in Indian women. The plasma concentrations of glycine and serine increased in the Indian women after methionine (in juice) load. A significant negative correlation between plasma B6 and homocysteine (r= −0.70), and plasma folate and glycine and serine levels were observed in the Indian group (P<0.05) but not in the American group. Conclusion Multi-nutrient insufficiency in the Indian women caused unique changes in markers of whole body protein and one carbon metabolism. These data would be useful in developing nutrient intervention strategies.

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Beyond lipids, pharmacological PPARα activation has important effects on amino acid metabolism as studied in the rat

Cited by 46 publications

References 40 publications

PPAR-α as a Key Nutritional and Environmental Sensor for Metabolic Adaptation

PPAR-α as a Key Nutritional and Environmental Sensor for Metabolic Adaptation

Hepatic Amino Acid-Degrading Enzyme Expression Is Downregulated by Natural and Synthetic Ligands of PPARα in Rats

Effect of multi-nutrient insufficiency on markers of one carbon metabolism in young women: response to a methionine load

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