PPAR alpha is a very important protein for metabolizing fat and for weight loss.
Intro to PPAR-alpha
I’ve spoken about PPAR gamma. This post is about its related kin PPAR alpha, which has somewhat different effects.
PPAR-alpha is a protein (transcription factor) that increases fat breakdown in the liver and elsewhere. A 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.
The Benefits of PPAR Alpha
Activation of PPAR-alpha promotes uptake, utilization, and breakdown of fatty acids by increasing genes involved in fatty acid transport, binding, activation, and oxidation.
Besides increasing fat utilization, it increases glucose production and bile synthesis/secretion .
PPAR-alpha is critical for normal responses to fasting. Without PPARa, there are major metabolic disturbances including low levels of ketone bodies, hypoglycemia, and fatty liver.
PPAR alpha helps with the detoxification of drugs and toxins .
PPAR alpha is protective against heart disease by inhibiting macrophage inflammation and increasing cholesterol efflux (via LXR and ABCA1) .
PPAR alpha activators have been shown to improve animal models of multiple sclerosis (EAE) .
PPAR-a can help increase IGF-1, which will help you build muscle. Mice without PPAR-alpha have 40% less IGF-1 .
PPAR alpha increases UCP-3 , which is important for fat loss. This and other mechanisms make PPAR alpha important for fat loss.
PPAR alpha increases MTHFR gene production .
PPAR alpha increases PXR , FGF-21 , CPT1A , HNF4, Catalase, and LXR–ABCA1 , UCP3 , MTP, FATP, MDR2 , SREBP1c .
Males vs Females: PPAR Alpha Increases Th2 Immunity and Suppresses Th1 Immunity
Males are more prone to Th17 dominance, while females are more prone to Th1 dominance .
This is because Androgens increase PPAR alpha, which causes inhibition of Th1 dominance. At the same time, men have lower PPAR gamma, which leads to Th17 dominance .
To some extent, Th1 and Th17 ‘compete’ with each other. IL-2 produced by Th1 cells activates STAT5, which competes with STAT3 (which produces Th17 dominance) .
PPAR Alpha Negatives
PPAR-a causes insulin resistance in the liver .
As mentioned, PPAR alpha can increase Th17 dominance .
How to Increase PPAR Alpha
Omega-6/Linoleic acid metabolites/Arachidonic acid, as well as other polyunsaturated fatty acids, are the main ways we naturally activate PPAR alpha .
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).
Unlike PPAR gamma, PPAR alpha has been found to be activated by both saturated and unsaturated fatty acids, such as oleic acid, palmitic acid, linoleic acid, and arachidonic acid .
PPAR alpha is also stimulated by stress, cortisol, and insulin .
- Pathways to activate PPAR alpha: SIRT1 , PGC-1a 
- Cold 
- Exercise 
- Sun/UVB (skin) 
- Fasting  – fasting increases SIRT1 via activation of PPAR-alpha in mice .
- DHEA 
- Zinc 
- Fish oil/DHA 
- R-Lipoic Acid 
- Hydroxytyrosol 
- Resveratrol 
- Cinnamon 
- EGCG [32, 33]
- Bitter melon 
- Epimedium/Icariin 
- Nicotinamide Riboside – NAD+ helps activate both PPAR-alpha and SIRT1 .
- Oregano – carvacrol , Biochanin A 
- Carnitine 
- Naringenin 
- PQQ 
- Genistein 
- Palmitoylethanolamide (PEA) 
- Lion’s Mane 
- Leukotriene B4
- Gynostemma 
- Anandamide 
- Fenofibrate (drug)
Circadian Control of PPAR Alpha
PPAR alpha has a circadian rhythm in several organs, including the heart, muscles, liver, and kidney .
PPAR alpha is controlled by the circadian CLOCK and BMAL1 genes. PPAR alpha increases BMAL1 and BMAL1 increases PPAR alpha .
PPAR alpha directly regulates the gene activity of Bmal1 and Rev-erb alpha. Per2 interacts with nuclear receptors including PPAR alpha and Rev-Erb alpha and serves as a co-regulator of nuclear receptor-mediated transcription .
Drugs that increase PPAR alpha also increase the production of and reset circadian expression of Bmal1, Per2, and Rev-erb alpha in mouse livers. These drugs can phase advance the rhythmic expression (cause it to start earlier) of Bmal1, Per2, and Rev-erb alpha in several mouse peripheral tissues .
PPAR Alpha Inhibitors
PPAR Alpha Gene
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