Our Livers SHRED omega 3 PUFA. For better or for worse.

Video Link First, tl;dw Summary Article Below


Omega 3 PUFA activate PPAR alpha, which in turn activates peroxisomes. This is what gives PPAR alpha the name Peroxisome Proliferator.

Dietary perilla oil (alpha-linolenic acid) and fish oil (long chain omega 3 PUFA) activate PPAR alpha, leading to massively increased peroxisomal fat oxidation in rat liver.

Peroxisomes carry out the process of beta-oxidation: breaking down long fat molecules into acetyl-CoA. Acetyl groups are 2 carbon units that are the building blocks of longer fats.

Peroxisomes can’t turn the acetyl-CoA into ATP – they don’t have an electron transport chain – so they export it. The exported acetyl-CoA can either be imported into the mitochondria to make ATP or it can be used in the cytoplasm to make fats, cholesterol and bile acids.

When PPAR alpha is activated, the result is an increase in both fat oxidation – fats being broken down into acetyl-CoA in the peroxisome and mitochondria – and lipogenesis – the rebuilding of the fats into mostly MUFA. You can see that fenofibrate – a pharmeceutical activator of PPAR alpha – increases expression of fat oxidation enzymes such as Aox (peroxisomal) and CPT-1a (mitochondrial). It also increases expression levels of enzymes involved in fat synthesis such as fatty acid synthase (Fas) and enzymes involved in creating MUFA such as Elovl6 and SCD1.

Activating PPAR alpha causes an increase in both breaking down (shredding) and building of fats. The shredding of fats is more activated in the peroxisomes, which favor long chain PUFA and branched fats. The building of fats favors oleic acid.

Activating PPAR alpha depletes PUFA and Increases Oleic acid

Fenofibrate causes a marked drop in PUFA (22:6n3, 18:2n6, 18:3n6) and a corresponding increase in MUFA (18:1n9 – oleic acid).

Getting rid of PUFA might sound great. In fact increased expression of the enzymes SCD1 and D6D are associated with massively increased risk of developing diabetes. (Kroger, 2011)

Fish Oil Kills Mice Lacking PPAR alpha

In addition to being involved in fat metabolism, PPAR alpha is also involved in detoxification pathways. If you remove the gene PPAR alpha from mice and feed them sufficient fish oil, they will be dead within two weeks due to acute liver failure.

This is a survival curve. Whenever the solid line drops, a fish-oil eating mouse who lacks PPAR alpha has perished.

Humans Have Less Peroxisome Activity Than Mice

Rodents eat PUFA-rich seeds and have high peroxisome activity. Humans evolved from fruit eating great apes who would’ve consumed little PUFA. Humans have lower baseline peroxisomal activity than rodents (and less ability to detoxify omega-3 PUFA) and human peroxisomal activity is increased less by PPAR alpha.

Maybe Don’t Eat PUFA?

Just a thought.

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1 thought on “Our Livers SHRED omega 3 PUFA. For better or for worse.”

  1. Great work, very interesting, thank you. Only one comment about your statement of lowering NADH by activating peroxisomes. Literature says the opposite is true in mouse model. It is part of the fat making setup, malonyl-CoA prevents saturated fats to go to mitochondria, so they are converted to unsaturated by SCD1 or wait, and high NADH prevent pyruvate to be oxidized in mitochondria, it is converted to glycerol to make fat droplets from triglycerides.
    It looks like this detox mechanism of converting PUFA to oleic acid prolongs life of worms by lowering oxidative stress. PUFA with double bonds on even positions possibly harm NNT anti-oxidation chain by using DECR enzyme that depletes NADPH in mitochondrial matrix. And peroxisomal H2O2 is mainly used to lower lipolysis, fat making is protective and safe if NNT system is not harmed by acetylation.

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