I wasn't going to torture lactate in the usual manner but Alan Couzens on Twitter suggested the two essentials for weight loss were to oxidise lipids and to minimise lactate. I was vaguely aware that lactate is a potent inhibitor of lipolysis and that rapidly rising lactate with exercise is going to tank your fatty acid availability. So I assumed lactate is an insulin mimetic and this is a quick hit searching Pubmed for lactate and lipolysis. GPR81 and HCAR1 are different names for the same receptor:
Lactate inhibits lipolysis in fat cells through activation of an orphan G-protein-coupled receptor, GPR81
which obviously suggests that this might be happening:
However there was nothing here to relate this to NADPH oxidases, so I added some more search terms and got this paper:
which is more interesting.
Recall that acetate primes NOX4 in neutrophils to be ready to protect you from severe sepsis? By phosphorylating it.
Lactate does something similar and allows me to add this part to the doodle:
This, in chondrocytes, is a positive feedback loop. When they want to to reject insulin signalling, they really will generate toxic levels of ROS, which will ruin your knees. I wonder if this positive feedback is a generic trait too. Okay, I'll leave lactate alone soon.
Interestingly, in people undergoing total knee replacement surgery serum lactate can be as high as 13mmol/l at rest. Even in "normal" controls one individual had a lactate of 9mmol/l at rest. One feature of metabolic syndrome seems to be that you walk around with the lactate levels of a young athlete under exercise while sitting still, even without a cup of sugary tea by your hand...
Fascinating.
Peter
3 comments:
So other than high exercise rates it seems that fructose(or ethanol) consumption would be what pushes lactate up.
I've never felt like I've had a firm grasp on how fructose consumption beyond the evolved human diet range messes things up.. I have:
Higher ROS
high Lactate
The ROS is likely to effect cancer rates?
Unnaturally high lactate might well screw up our joints. ( How would we know if such damage is caused by ROS vs lactate?).
Karl: mostly in the liver eg figure 1 here
https://acutecaretesting.org/en/articles/increased-blood-lactate-levels-a-marker-of
Pyruvate DeHydrogenase is in turn activated by Pyruvate DeHydrogenase Phosphatase ( pdhp) I don't know what regulates that, or what regulates Lactate DeHydrogenase.
I would guess that pdhp is somehow governed by atp status so that if atp is high then not much pyruvate gets converted to AcCoA. In this situation in the face of high glucose pressure perhaps pyruvate is mostly converted to lactate which exits into the bloodstream.
I bet it's not really that simple.
I can vouch for diverse and painful arthritises in the context of MetSyn. IRC metformin helps.
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