Differential regulation of the human versus the mouse apolipoprotein AV gene by PPARalpha

Prieur, Xavier; Lesnik, Philippe; Moreau, Martine; Rodríguez, Joaquín; Doucet, Chantal; Chapman, M. John; Huby, Thierry

doi:10.1016/j.bbalip.2009.03.015

Cited by 15 publications

(5 citation statements)

References 45 publications

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“…Consistent with this finding, APOA5 mRNA is induced by PPARα activation in human and monkey hepatocytes, and APOA5 plasma levels are increased by treatment of monkeys with a synthetic PPARα agonist [173,253,254]. In contrast, Apoa5 upregulation is not observed in mouse liver or in cultured mouse hepatocytes, presumably due to a degenerate and non-functional PPRE in the mouse Apoa5 promoter [255]. Surprisingly, we found that Apoa5 mRNA is markedly and reproducibly induced by Wy14643 in mouse liver slices (our unpublished data), suggesting that Apoa5 may be a PPARα target in mouse after all, perhaps via the use of an alternative PPAR response element.…”

Section: Target Genes and Pathways Of Pparαmentioning

confidence: 84%

Integrated physiology and systems biology of PPARα

Kersten

2014

Molecular Metabolism

516

415

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The Peroxisome Proliferator Activated Receptor alpha (PPARα) is a transcription factor that plays a major role in metabolic regulation. This review addresses the functional role of PPARα in intermediary metabolism and provides a detailed overview of metabolic genes targeted by PPARα, with a focus on liver. A distinction is made between the impact of PPARα on metabolism upon physiological, pharmacological, and nutritional activation. Low and high throughput gene expression analyses have allowed the creation of a comprehensive map illustrating the role of PPARα as master regulator of lipid metabolism via regulation of numerous genes. The map puts PPARα at the center of a regulatory hub impacting fatty acid uptake, fatty acid activation, intracellular fatty acid binding, mitochondrial and peroxisomal fatty acid oxidation, ketogenesis, triglyceride turnover, lipid droplet biology, gluconeogenesis, and bile synthesis/secretion. In addition, PPARα governs the expression of several secreted proteins that exert local and endocrine functions.

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Section: Target Genes and Pathways Of Pparαmentioning

confidence: 84%

Integrated physiology and systems biology of PPARα

Kersten

2014

Molecular Metabolism

516

415

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“…There are some limitations of our study which should be considered. In general, although major parts of the lipid metabolism appear to be conserved between mice and humans, differences exist regarding the regulation of triglyceride levels via apolipoproteins such as APOA5 [ 56 ] or the target genes of PPARα, the master regulator of hepatic lipid metabolism [ 57 ]. Moreover, similarities and differences in BAT between mice and humans relating to metabolism and thermogenesis as well as their underlying mechanisms of regulation are still not well understood.…”

Section: Discussionmentioning

confidence: 99%

Dietary n-3 long-chain polyunsaturated fatty acids upregulate energy dissipating metabolic pathways conveying anti-obesogenic effects in mice

et al. 2018

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BackgroundWe previously reported on the anti-obesogenic and anti-inflammatory effects associated with n-3 long-chain polyunsaturated fatty acids (LCPUFA) in our diet-induced obesity (DIO) mouse model. Two isocaloric high-fat diets (HFDs; 48 kJ% fat), HFD (HF) and n-3 LCPUFA-enriched HFD (HF/n-3), and a control diet (C; 13 kJ% fat) were used. The underlying mechanisms however have largely remained unclear. Here, we assessed whether the reduced fat mass reflected n-3 LCPUFA-induced expression changes in lipid metabolism of the intestine, liver, and interscapular brown adipose tissue (iBAT), as well as increased iBAT thermogenic capacity.MethodsFor HF/n-3, saturated and monounsaturated fatty acids were partially substituted by n-3 LCPUFA eicosapentaenoic acid and docosahexaenoic acid to achieve a balanced n-6/n-3 PUFA ratio (0.84) compared to the unbalanced ratios of HF (13.5) and C (9.85). Intestine, liver and iBAT from male C57BL/6 J mice, fed defined soybean/palm oil-based diets for 12 weeks, were further analysed. Gene and protein expression analyses, immunohistochemistry and correlation analyses for metabolic interactions were performed.ResultsCompared to HF and C, our analyses suggest significantly diminished de novo lipogenesis (DNL) and/or increased hepatic and intestinal fatty acid oxidation (ω-oxidation and peroxisomal β-oxidation) in HF/n-3 mice. For iBAT, the thermogenic potential was enhanced upon HF/n-3 consistent with upregulated expression for uncoupling protein-1 and genes involved in mitochondrial biogenesis. In addition, a higher capacity for the supply and oxidation of fatty acids was observed and expression and correlation analyses indicated a coordinated regulation of energy metabolism and futile cycling of triacylglycerol (TAG). Moreover, HF/n-3 significantly increased the number of anti-inflammatory macrophages and eosinophils and significantly enhanced the levels of activated AMP-activated protein kinase α (AMPKα), peroxisome proliferator-activated receptor α (PPARα) and fibroblast growth factor 21 (FGF21).ConclusionsOur data suggest that by targeting transcriptional regulatory pathways, AMPKα, and FGF21 as potential mediators, HF/n-3 activated less efficient pathways for energy production, such as peroxisomal β-oxidation, increased ATP consumption upon the induction of futile cycling of TAG, and additionally increased the thermogenic and oxidative potential of iBAT. Therefore, we consider n-3 LCPUFA as the potent inducer for upregulating energy dissipating metabolic pathways conveying anti-obesogenic effects in mice.Electronic supplementary materialThe online version of this article (10.1186/s12986-018-0291-x) contains supplementary material, which is available to authorized users.

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“…In addition, administration of a potent and selective PPARα agonist, LY570977 l -lysine decreased TG and increased circulating apoA-V levels in cynomolgus monkeys [41]. Functional PPAR-binding element in the promoter of the human APOA5 gene was found in human, which is somewhat degenerate and non-functional in the corresponding mouse Apoa5 [34]. APOA5 resides on the APOAI/CIII/AIV gene cluster on human 11q23 [33].…”

Section: Discussionmentioning

confidence: 99%

Gene expression profiles in human HepG2 cells treated with extracts of the Tamarindus indica fruit pulp

2010

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Tamarindus indicaL. (T. indica) or locally known as asam jawa belongs to the family of Leguminosae. The fruit pulp had been reported to have antioxidant activities and possess hypolipidaemic effects. In this study, we attempted to investigate the gene expression patterns in human hepatoma HepG2 cell line in response to treatment with low concentration of the fruit pulp extracts. Microarray analysis using Affymetrix Human Genome 1.0 S.T arrays was used in the study. Microarray data were validated using semi-quantitative RT–PCR and real-time RT–PCR. Amongst the significantly up-regulated genes were those that code for the metallothioneins (MT1M, MT1F, MT1X) and glutathione S-transferases (GSTA1, GSTA2, GST02) that are involved in stress response. APOA4, APOA5, ABCG5 and MTTP genes were also significantly regulated that could be linked to hypolipidaemic activities of the T. indica fruit pulp.

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Differential regulation of the human versus the mouse apolipoprotein AV gene by PPARalpha

Cited by 15 publications

References 45 publications

Integrated physiology and systems biology of PPARα

Integrated physiology and systems biology of PPARα

Dietary n-3 long-chain polyunsaturated fatty acids upregulate energy dissipating metabolic pathways conveying anti-obesogenic effects in mice

Gene expression profiles in human HepG2 cells treated with extracts of the Tamarindus indica fruit pulp

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