> On Jul 15, 4:06 am, Olafur Pall Olafsson <olafurp...@yahoo.com> wrote:
>
> > Fasting increases PPARalpha, as do several PPARalpha agonists such as
> > fish oil, sesamin, green tea and lipoic acid.
>
> Having a low body fat should also help increase PPARalpha since
> adiponectin (which is increases once body fat decreases) appears to be
> able to activate PPARalphahttp://pmid.us/18309113.
>
>
>
> > J Biol Chem. 2004 Dec 10;279(50):52390-8. Epub 2004 Sep 15.
> > Related Articles, Links
> > Click here to read
> > The transcriptional response to a peroxisome proliferator-
> > activated receptor alpha agonist includes increased expression of
> > proteome maintenance genes.
>
> > Anderson SP, Howroyd P, Liu J, Qian X, Bahnemann R, Swanson C,
> > Kwak MK, Kensler TW, Corton JC.
>
> > Investigative Toxicology and Pathology Group, Safety Assessment,
> > GlaxoSmithKline Research and Development, Research Triangle Park,
> > North Carolina 27709, USA.
>
> > The nuclear receptor peroxisome proliferator-activated receptor
> > alpha (PPARalpha), in addition to regulating lipid homeostasis,
> > controls the level of tissue damage after chemical or physical stress.
> > To determine the role of PPARalpha in oxidative stress responses, we
> > examined damage after exposure to chemicals that increase oxidative
> > stress in wild-type or PPARalpha-null mice. Primary hepatocytes from
> > wild-type but not PPARalpha-null mice pretreated with the PPAR pan-
> > agonist WY-14,643 (WY) were protected from damage to cadmium and
> > paraquat. The livers from intact wild-type but not PPARalpha-null mice
> > were more resistant to damage after carbon tetrachloride treatment. To
> > determine the molecular basis of the protection by PPARalpha, we
> > identified by transcript profiling genes whose expression was altered
> > by a 7-day exposure to WY in wild-type and PPARalpha-null mice. Of the
> > 815 genes regulated by WY in wild-type mice (p < or = 0.001; > or =1.5-
> > fold or < or =-1.5-fold), only two genes were regulated similarly by
> > WY in PPARalpha-null mice. WY increased expression of stress modifier
> > genes that maintain the health of the proteome, including those that
> > prevent protein aggregation (heat stress-inducible chaperones) and
> > eliminate damaged proteins (proteasome components). Although the
> > induction of proteasomal genes significantly overlapped with those
> > regulated by 1,2-dithiole-3-thione, an activator of oxidant-inducible
> > Nrf2, WY increased expression of proteasomal genes independently of
> > Nrf2. Thus, PPARalpha controls the vast majority of gene expression
> > changes after exposure to WY in the mouse liver and protects the liver
> > from oxidant-induced damage, possibly through regulation of a distinct
> > set of proteome maintenance genes.
>
> > Publication Types:
>
> > * In Vitro
> > * Research Support, U.S. Gov't, P.H.S.
>
> > PMID: 15375163 [PubMed - indexed for MEDLINE]
>
> > Related Articles
>
> > * Overlapping transcriptional programs regulated by the
> > nuclear receptors peroxisome proliferator-activated receptor alpha,
> > retinoid X receptor, and liver X receptor in mouse liver. [Mol
> > Pharmacol. 2004]
> > * Time course investigation of PPARalpha- and Kupffer cell-
> > dependent effects of WY-14,643 in mouse liver using microarray gene
> > expression. [Toxicol Appl Pharmacol. 2007]
> > * Toxic effects of fumonisin in mouse liver are independent of
> > the peroxisome proliferator-activated receptor alpha. [Toxicol Sci.
> > 2006]
> > * Identification of novel peroxisome proliferator-activated
> > receptor alpha (PPARalpha) target genes in mouse liver using cDNA
> > microarray analysis. [Gene Expr. 2001]
> > * Activation of peroxisome proliferator-activated receptor
> > alpha increases the expression and activity of microsomal triglyceride
> > transfer protein in the liver. [J Biol Chem. 2005]
> > * » See all Related Articles...
>
> Relevant to this the long-lived Snell dwarf mice appear to have
> consitutively increased expression of PPARalpha.
>
> Mol Pharmacol. 2005 Mar;67(3):681-94. Epub 2004 Dec 2.
> Related Articles, Links
> Click here to read
> Constitutive expression of peroxisome proliferator-activated
> receptor alpha-regulated genes in dwarf mice.
>
> Stauber AJ, Brown-Borg H, Liu J, Waalkes MP, Laughter A, Staben
> RA, Coley JC, Swanson C, Voss KA, Kopchick JJ, Corton JC.
>
> CIIT Centers for Health Research, Research Triangle Park, North
> Carolina, USA.
>
> Defects in growth hormone secretion or signaling in mice are
> associated with decreased body weights (dwarfism), increased
> longevity, increased resistance to stress, and decreases in factors
> that contribute to cardiovascular disease and cancer. Peroxisome
> proliferators (PP) alter a subset of these changes in wild-type mice
> through activation of the nuclear receptor family member PP-activated
> receptor alpha (PPARalpha). We tested the hypothesis that an overlap
> in the transcriptional programs between untreated dwarf mice and PP-
> treated wild-type mice underlies these similarities. Using transcript
> profiling, we observed a statistically significant overlap in the
> expression of genes differentially regulated in control Snell dwarf
> mice (Pit-1dw) compared with phenotypically normal heterozygote (+/dw)
> control mice and those altered by the PP 4-chloro-6-(2,3-xylidino)-2-
> pyrimidinyl)thioacetic acid (WY-14,643) in +/dw mice. The genes
> included those involved in beta- and omega-oxidation of fatty acids
> (Acox1, Cyp4a10, Cyp4a14) and those involved in stress responses (the
> chaperonin, T-complex protein1epsilon) and cardiovascular disease
> (fibrinogen). The levels of some of these gene products were also
> altered in other dwarf mouse models, including Ames, Little, and
> growth hormone receptor-null mice. The constitutive increases in
> PPARalpha-regulated genes may be partly caused by increased expression
> of PPARalpha mRNA and protein as observed in the livers of control
> Snell dwarf mice. These results indicate that some of the beneficial
> effects associated with the dwarf phenotype may be caused by
> constitutive activation of PPARalpha and regulated genes.
>
> PMID: 15576629 [PubMed - indexed for MEDLINE]
>
> Related Articles
>
> * Overlapping transcriptional programs regulated by the
> nuclear receptors peroxisome proliferator-activated receptor alpha,
> retinoid X receptor, and liver X receptor in mouse liver. [Mol
> Pharmacol. 2004]
> * The transcriptional response to a peroxisome proliferator-
> activated receptor alpha agonist includes increased expression of
> proteome maintenance genes. [J Biol Chem. 2004]
> * Role of the peroxisome proliferator-activated receptor alpha
> (PPARalpha) in responses to trichloroethylene and metabolites,
> trichloroacetate and dichloroacetate in mouse liver. [Toxicology.
> 2004]
> * Developmental and tissue-specific involvement of peroxisome
> proliferator-activated receptor-alpha in the control of mouse
> uncoupling protein-3 gene expression. [Endocrinology. 2006]
> * Role of the peroxisome proliferator-activated receptor alpha
> in responses to diisononyl phthalate. [Toxicology. 2003]
> * » See all Related Articles...
>
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>
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>
> The full text is free:http://molpharm.aspetjournals.org/cgi/content/full/67/3/681
>
> Here is a quote from the discussion section of the full text:
>
> "These studies provide evidence that growth hormone negatively
> regulates PPAR{alpha} in the intact animal through activation of
> STAT5b."
>
> "PPAR{alpha} may play roles in other models of stress resistance and/
> or longevity. Using comprehensive transcript profiling, PPAR{alpha}
> was required for ~20% of the gene expression changes in the liver
> after a 5-week caloric restriction (CR) and is required for CR to
> protect the liver from a lethal dose of thioacetamide, a hepatotoxic
> agent (Corton et al., 2004Go). As in the livers of Snell dwarf mice,
> the PPAR{alpha}-dependent CR genes included those involved in fatty
> acid metabolism (i.e., Cyp4a10, Cyp4a14). With our findings of
> increased expression of PPAR{alpha}-dependent genes in dwarf mice,
> alterations in PPAR{alpha} target gene regulation seems to be common
> in many animal models of longevity and/or stress resistance. A dwarf
> mouse strain in which the PPAR{alpha} gene is inactivated will be
> important to unequivocally establish PPAR{alpha}'s role in the
> beneficial effects associated with defects in growth hormone
> signaling."
Olafur Pall Ol…
