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Home › Dataset Library › Transcription profiling of mouse PPARalpha knockouse to investigate TPPARalpha-mediated effects of dietary lipids on intestinal barrier...

Dataset: Transcription profiling of mouse PPARalpha knockouse to investigate TPPARalpha-mediated effects of dietary lipids on intestinal barrier gene expression

Background: The selective absorption of nutrients and other food constituents in the small intestine is mediated by a group of transport...

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Background: The selective absorption of nutrients and other food constituents in the small intestine is mediated by a group of transport proteins and metabolic enzymes, often collectively called ‘intestinal barrier proteins’. An important receptor that mediates the effects of dietary lipids on gene expression is the peroxisome proliferator-activated receptor alpha (PPARα), which is abundantly expressed in enterocytes. In this study we examined the effects of acute nutritional activation of PPARα on expression of genes encoding intestinal barrier proteins. To this end we used triacylglycerols composed of identical fatty acids in combination with gene expression profiling in wild-type and PPARα-null mice. Treatment with the synthetic PPARα agonist WY14643 served as reference. Results: We identified 74 barrier genes that were PPARα-dependently regulated 6 hours after activation with WY14643. For eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and oleic acid (OA) these numbers were 46, 41, and 19, respectively. The overlap between EPA-, DHA-, and WY14643-regulated genes was considerable, whereas OA treatment showed limited overlap. Functional implications inferred form our data suggested that nutrient-activated PPARα regulated transporters and phase I/II metabolic enzymes were involved in a) fatty acid oxidation, b) cholesterol, glucose, and amino acid transport and metabolism, c) intestinal motility, and d) oxidative stress defense. Conclusion: We identified intestinal barrier genes that were PPARα-dependently regulated after acute activation by fatty acids.This knowledge provides a better understanding of the impact dietary fat has on the barrier function of the gut, identifies PPARα as an important factor controlling this key function, and underscores the importance of PPARα for nutrient-mediated gene regulation in intestine. Experiment Overall Design: Pure bred wild-type (129S1/SvImJ) and PPARα-null (129S4/SvJae) mice were treated for 6 hours with the synthetic triacylglycerols triolein [oleic acid (OA, C18:1)], trieicosapentaenoin [eicosapentaenoic acid (EPA, C20:5)] or tridocosahexaenoin [ocosahexaenoic acid (DHA, C22:6)], or the potent PPARα agonist WY14,643. Two weeks before the start of the experiment, mice were put on a modified AIN76A diet, in which corn oil was replaced by olive oil. At the day of the experiment mice were fasted for four hours. At 9 AM mice were dosed by oral gavage with 400 µl of a 0.1% WY14643 suspension in 0.5% carboxymethyl cellulose, or 400 µl of the synthetic triacylglycerols. Six hours after the gavage the mice were anaesthetized, small intestines were removed, flushed with ice-cold PBS and remaining fat and pancreatic tissue was carefully removed. Total RNA was then isolated. RNA of 4-5 biological replicates was hybridized to Affymetrix 430-2.0 plus arrays. Five microgram total RNA was labelled according to the ENZO-protocol, fragmented and hybridized according to Affymetrix's protocols.

Species:
mouse

Samples:
35

Source:
E-GEOD-9533

PubMed:
18489776

Updated:
Dec.12, 2014

Registered:
Nov.21, 2014


Factors: (via ArrayExpress)
Sample
GSE9533GSM241424
GSE9533GSM241425
GSE9533GSM241426
GSE9533GSM241427
GSE9533GSM241416
GSE9533GSM241417
GSE9533GSM241418
GSE9533GSM241419
GSE9533GSM241407
GSE9533GSM241408
GSE9533GSM241409
GSE9533GSM241410
GSE9533GSM241401
GSE9533GSM241397
GSE9533GSM241398
GSE9533GSM241399
GSE9533GSM241400
GSE9533GSM241420
GSE9533GSM241421
GSE9533GSM241422
GSE9533GSM241423
GSE9533GSM241411
GSE9533GSM241412
GSE9533GSM241413
GSE9533GSM241414
GSE9533GSM241415
GSE9533GSM241402
GSE9533GSM241403
GSE9533GSM241404
GSE9533GSM241405
GSE9533GSM241406
GSE9533GSM241393
GSE9533GSM241394
GSE9533GSM241395
GSE9533GSM241396

Tags

  • amino acid
  • cellulose
  • fatty acid
  • glucose
  • gut
  • intestine
  • peroxisome
  • small intestine

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