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  3. PPARA

PPARA (Peroxisome proliferator activated receptor alpha)

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Summary of PPARA

PPAR alpha is a very important protein for metabolizing fat and glucose, which helps with weight loss. It alters the expression of a large number of genes. It's important for energy production. 

Mice lacking PPAR-alpha have an impaired response to fasting, including low levels of ketone bodies, hypoglycemia, and fatty liver. PPAR-alpha increases bile synthesis/secretion (R).

PPAR alpha inhibits inflammation and animal models of autoimmune conditions such as Multiple Sclerosis (R). PPAR-a can help increase IGF-1, which will help you build muscle (R).

PPAR-alpha is a protein (transcription factor) that increases fat breakdown in the liver and elsewhere.  Good metabolism is important for energy production.

PPAR-alpha alters the expression of a large number of genes. PPAR-alpha is activated under conditions of calorie restriction and is necessary for the process of ketogenesis, a key adaptive response to prolonged fasting .

PPAR-alpha is mainly found in the liver and brown fat, followed by the heart and kidney. Lower PPAR-alpha expression levels are found in the small and large intestine, muscle and adrenal gland.

Activation of PPAR-alpha promotes uptake, utilization, and breakdown of fatty acids by increasing genes involved in fatty acid transport, binding, activation, and oxidation.

Mice lacking PPAR-alpha have an impaired response to fasting, characterized by major metabolic disturbances including low levels of ketone bodies, hypoglycemia, and fatty liver. PPAR-alpha is at the core of fat utilization, as well glucose production and bile synthesis/secretion (R).

PPAR alpha inhibits animal models of autoimmune conditions such as MS (R). PPAR alpha is protective against heart disease by inhibiting macrophage inflammation and increasing cholesterol efflux (via LXR and ABCA1) (R).

Read: About PPAR Alpha and Natural Ways To Activate It.

It's better to have this gene increased most of the time.
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Protein names

Recommended name:

Peroxisome proliferator-activated receptor alpha

Alternative name(s):

PPAR-alpha
Nuclear receptor subfamily 1 group C member 1

PPARA SNPs

    To see your genotype, you should be logged in and have a file with your genotype uploaded.

  1. RS135551 (PPARA) ??
  2. RS1800206 (PPARA) ??
  3. RS4253623 (PPARA) ??
  4. RS4253655 (PPARA) ??
  5. RS4253728 (PPARA) ??
  6. RS4253772 (PPARA) ??
  7. RS4823613 (PPARA) ??
  8. RS9615264 (PPARA) ??

Top Gene-Substance Interactions

PPARA Interacts with These Diseases

Disease Score

Fixes

Omega-6/Linoleic acid metabolites/Arachidonic acid, as well as other polyunsaturated fatty acids, are the main ways we naturally activate PPAR alpha (R). This is probably why omega-6's have some benefits in various studies.

It's good to get a good balance of DHA/EPA, MUFAs and Omega 6's, with some saturated fat (not excess like some paleo recommends). PPAR alpha is also stimulated by stress, cortisol, and insulin (R).

PPARa is activated by oleylethanolamide, a naturally occurring lipid that regulates satiety.

My favorite ways to increase PPAR-alpha:

  • Cold (R)
  • Exercise (R),
  • Fasting (R) - fasting increases SIRT1 via activation of PPAR-alpha in mice (R).
  • Fish oil/DHA (R),
  • Hydroxytyrosol (R),
  • Cinnamon (R)

​Other ways to increase PPAR-alpha:

  • Resveratrol (R),
  • R-Lipoic Acid (R), 
  • Epimedium/Icariin (R, R2),
  • Nicotinamide Riboside (R).
  • Carvacrol/Oregano oil (R),
  • Oregano/Biochanin A (R) - oregano has a few chemicals that help activate PPAR alpha,
  • Carnitine (R),
  • Naringenin (R)
  • PQQ (R),
  • Genistein (R),

Substances That Increase PPARA

Substances Interaction Organism Category

Substances That Decrease PPARA

Substances Interaction Organism Category

Advanced Summary

May be required for the propagation of clock information to metabolic pathways regulated by PER2.

PPAR-a inhibits COX2 (R). PPAR-a can help increase IGF-1, which will help you build muscle.  Mice without PPAR-alpha have 40% less IGF-1 (R). Mice without PPAR alpha have 20X less UCP-3 (R), which is important for fat loss.  This and other mechanisms make PPAR alpha important for fat loss. PPAR-a causes insulin resistance in the liver (R).

Conditions with Increased Gene Activity

Condition Change (log2fold) Comparison Species Experimental variables Experiment name

Conditions with Decreased Gene Activity

Condition Change (log2fold) Comparison Species Experimental variables Experiment name

Technical

The following transcription factors affect gene expression:

  • ER-alpha
  • PPAR-gamma1
  • PPAR-gamma2
  • AP-1
  • c-Jun
  • PPAR-alpha
  • C/EBPalpha
  • HNF-4alpha1
  • HNF-4alpha2
  • STAT5B
  • SIRT1
  • PGC-1alpha
  • RXR-alpha

Tissue specificity:

Skeletal muscle, liver, heart and kidney.

Gene Pathways:

  • Adipocytokine signaling pathway
  • Mus musculus biological processes
  • PPAR signaling pathway
  • Gene Expression
  • Circadian Clock
  • Metabolism
  • Hepatitis C

Molecular Function:

  • Dna Binding
  • Drug Binding
  • Lipid Binding
  • Rna Polymerase Ii Core Promoter Proximal Region Sequence-Specific Dna Binding
  • Rna Polymerase Ii Repressing Transcription Factor Binding
  • Rna Polymerase Ii Transcription Factor Activity, Ligand-Activated Sequence-Specific Dna Binding
  • Sequence-Specific Dna Binding
  • Steroid Hormone Receptor Activity
  • Transcriptional Activator Activity, Rna Polymerase Ii Core Promoter Proximal Region Sequence-Specific Binding
  • Transcriptional Activator Activity, Rna Polymerase Ii Transcription Factor Binding
  • Transcriptional Repressor Activity, Rna Polymerase Ii Core Promoter Proximal Region Sequence-Specific Binding
  • Transcription Factor Activity, Sequence-Specific Dna Binding
  • Transcription Factor Binding
  • Ubiquitin Conjugating Enzyme Binding
  • Zinc Ion Binding

Biological Processes:

  • Behavioral Response To Nicotine
  • Cellular Lipid Metabolic Process
  • Circadian Regulation Of Gene Expression
  • Enamel Mineralization
  • Epidermis Development
  • Fatty Acid Metabolic Process
  • Fatty Acid Transport
  • Heart Development
  • Lipid Metabolic Process
  • Lipoprotein Metabolic Process
  • Negative Regulation Of Appetite
  • Negative Regulation Of Blood Pressure
  • Negative Regulation Of Cholesterol Storage
  • Negative Regulation Of Glycolytic Process
  • Negative Regulation Of Inflammatory Response
  • Negative Regulation Of Leukocyte Cell-Cell Adhesion
  • Negative Regulation Of Macrophage Derived Foam Cell Differentiation
  • Negative Regulation Of Neuron Death
  • Negative Regulation Of Pri-Mirna Transcription From Rna Polymerase Ii Promoter
  • Negative Regulation Of Receptor Biosynthetic Process
  • Negative Regulation Of Sequestering Of Triglyceride
  • Negative Regulation Of Transcription From Rna Polymerase Ii Promoter
  • Negative Regulation Of Transcription Regulatory Region Dna Binding
  • Positive Regulation Of Fatty Acid Beta-Oxidation
  • Positive Regulation Of Fatty Acid Oxidation
  • Positive Regulation Of Gluconeogenesis
  • Positive Regulation Of Transcription, Dna-Templated
  • Positive Regulation Of Transcription From Rna Polymerase Ii Promoter
  • Regulation Of Cellular Ketone Metabolic Process By Positive Regulation Of Transcription From Rna Polymerase Ii Promoter
  • Regulation Of Circadian Rhythm
  • Regulation Of Glycolytic Process By Positive Regulation Of Transcription From Rna Polymerase Ii Promoter
  • Regulation Of Lipid Transport By Positive Regulation Of Transcription From Rna Polymerase Ii Promoter
  • Response To Hypoxia
  • Response To Insulin
  • Transcription Initiation From Rna Polymerase Ii Promoter
  • Wound Healing

Drug Bank:

  • Clofibrate
  • Fenofibrate
  • Indomethacin
  • Bezafibrate
  • Gemfibrozil
*synonyms

Synonyms/Aliases/Alternative Names of the Gene:

hypothetical protein| A306_09110| AS27_11125| AS28_05074| CB1_000279020| GW7_17096| hPPAR| I79_022390| M959_01557| N300_02636| N301_16295| N302_12191| N303_11820| N305_11537| N306_00288| N307_10240| N308_04035| N309_00925| N310_03105| N311_12347| N312_11827| N320_00439| N321_04916| N322_02512| N324_01907| N326_01698| N327_00721| N328_04523| N329_07647| N330_03715| N331_00903| N332_07059| N333_00638| N334_10039| N335_10204| N336_04492| N340_10965| N341_05483| NR1C1| nuclear receptor subfamily 1 group C member 1| PAL_GLEAN10007134| PANDA_011925| peroxisome proliferative activated receptor, alpha| peroxisome proliferator-activated nuclear receptor alpha variant 3| peroxisome proliferator-activated receptor alpha| peroxisome proliferator-activated receptor alpha 2| peroxisome proliferator-activated receptor delta| peroxisome proliferator activator receptor alpha| peroxisomer proliferator activated receptor alpha| PPAR| ppara2| PPARalpha| PPAR-alpha| PPAR ALPHA| PPAR alpha protein| PPARD| proliferator-activated receptor alpha| TREES_T100014453| UY3_05588| XELAEV_18019740mg| xppara| xPPARalpha| xPPAR alpha| Y1Q_000473| Y956_09120| Z169_15640| ppara

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