Cocoa Butter and Safflower Oil Elicit Different Effects on Hepatic Gene Expression and Lipid Metabolism in Rats

Gustavsson, Catharina; Parini, Paolo; Ostojic, Jovanca; Cheung, Louisa; Hu, Jin; Zadjali, Fahad; Tahir, Faheem; Brismar, Kerstin; Norstedt, Gunnar; Tollet-Egnell, Petra

doi:10.1007/s11745-009-3352-0

Cited by 8 publications

(12 citation statements)

References 86 publications

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“…Therefore, fatty acids may play the dual role of gene expression activators of fatty acid oxidation and gene repressors of amino acid oxidation via PPARa. Recent data using microarray analysis in the liver of rats fed high-fat diets show a decrease in the expression of Hal and Sdh and a simultaneous increase in the rate of fatty acid oxidation (44). Therefore, our results strongly support the essential role that PPARa may play in the regulation of the gene expression of AADEs in the protein-sparing effect.…”

Section: Discussionsupporting

confidence: 84%

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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Section: Discussionsupporting

confidence: 84%

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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“…Microarrays containing 70 mer oligonucleotide probes for 27 649 rat protein-coding genes were fabricated and used to obtain transcript profiles, as described previously [22]. Each hybridisation compared Cy3-labeled cDNA reverse transcribed from RNA isolated from female rat livers with Cy5-labeled cDNA isolated from male livers.…”

Section: Methodsmentioning

confidence: 99%

Sex-different hepatic glycogen content and glucose output in rats

et al. 2010

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BackgroundGenes involved in hepatic metabolism have a sex-different expression in rodents. To test whether male and female rat livers differ regarding lipid and carbohydrate metabolism, whole-genome transcript profiles were generated and these were complemented by measurements of hepatic lipid and glycogen content, fatty acid (FA) oxidation rates and hepatic glucose output (HGO). The latter was determined in perfusates from in situ perfusion of male and female rat livers. These perfusates were also analysed using nuclear magnetic resonance (NMR) spectroscopy to identify putative sex-differences in other liver-derived metabolites. Effects of insulin were monitored by analysis of Akt-phosphorylation, gene expression and HGO after s.c. insulin injections.ResultsOut of approximately 3 500 gene products being detected in liver, 11% were significantly higher in females, and 11% were higher in males. Many transcripts for the production of triglycerides (TG), cholesterol and VLDL particles were female-predominant, whereas genes for FA oxidation, gluconeogenesis and glycogen synthesis were male-predominant. Sex-differences in mRNA levels related to metabolism were more pronounced during mild starvation (12 h fasting), as compared to the postabsorptive state (4 h fasting). No sex-differences were observed regarding hepatic TG content, FA oxidation rates or blood levels of ketone bodies or glucose. However, males had higher hepatic glycogen content and higher HGO, as well as higher ratios of insulin to glucagon levels. Based on NMR spectroscopy, liver-derived lactate was also higher in males. HGO was inhibited by insulin in parallel with increased phosphorylation of Akt, without any sex-differences in insulin sensitivity. However, the degree of Thr172-phosphorylated AMP kinase (AMPK) was higher in females, indicating a higher degree of AMPK-dependent actions.ConclusionsTaken together, males had higher ratios of insulin to glucagon levels, higher levels of glycogen, lower degree of AMPK phosphorylation, higher expression of gluconeogenic genes and higher hepatic glucose output. Possibly these sex-differences reflect a higher ability for the healthy male rat liver to respond to increased energy demands.

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“…Microarrays containing 70 mer oligonucleotide probes for 27 649 rat protein-coding genes were fabricated and used to obtain transcript profiles, essentially as described earlier (Gustavsson et al 2009). Each hybridisation compared fluorescent dye (e.g.…”

Section: Expression Profiling Using Microarraysmentioning

confidence: 99%

“…Total hepatic RNA was isolated, cDNA generated and gene expression quantified, as described earlier (Gustavsson et al 2009). The primers for the genes of interest are shown in Table 2.…”

Section: Analysis Of Gene Expression By Real-time Quantitative Rt-pcrmentioning

confidence: 99%

Sex-dependent hepatic transcripts and metabolites in the development of glucose intolerance and insulin resistance in Zucker diabetic fatty rats

Gustavsson

Soga²,

Wahlström

et al. 2011

Journal of Molecular Endocrinology

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Male Zucker diabetic fatty (mZDF) rats spontaneously develop type 2 diabetes, whereas females only become diabetic when fed a diabetogenic high-fat diet (high-fat-fed female ZDF rat, HF-fZDF). The aim of this study was to investigate if differences in liver functions could provide clues to this sex difference. Non-diabetic obese fZDF rats were compared with either mZDF or HF-fZDF regarding hepatic molecular profiles, to single out those components that might be protective in the females. High-fat feeding in fZDF led to enhanced weight gain, increased blood glucose and insulin levels, reduced insulin sensitivity and a trend towards reduced glucose tolerance, indicative of a prediabetic state. mZDF rats were diabetic, with low levels of insulin, high levels of glucose, reduced insulin sensitivity and impaired glucose tolerance. Transcript profiling and capillary electrophoresis time-of-flight mass spectrometry were used to indentify hepatic transcripts and metabolites that might be related to this. Many diet-induced alterations in transcript and metabolite levels in female rats were towards a 'male-like' phenotype, including reduced lipogenesis, increased fatty acid (FA) oxidation and increased oxidative stress responses. Alterations detected at the level of hepatic metabolites, indicated lower capacity for glutathione (GSH) production in male rats, and higher GSH turnover in females. Taken together, this could be interpreted as if anabolic pathways involving lipogenesis and lipid output might limit the degree of FA oxidation and oxidative stress in female rats. Together with a greater capacity to produce GSH, these hepatic sex differences might contribute to the sex-different development of diabetes in ZDF rats.

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Cocoa Butter and Safflower Oil Elicit Different Effects on Hepatic Gene Expression and Lipid Metabolism in Rats

Cited by 8 publications

References 86 publications

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

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

Sex-different hepatic glycogen content and glucose output in rats

Sex-dependent hepatic transcripts and metabolites in the development of glucose intolerance and insulin resistance in Zucker diabetic fatty rats

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