Thread by @martinsipx

Susceptibility to sunburns on high n-6 diets:

"UVB and H2O2 induced G2A expression and caused oxidation of linoleate to produce 9-HODE in HaCaT cells. [This] suggests that 9-HODE-G2A signaling plays proinflammatory roles in skin under oxidative conditions."

G2A Plays Proinflammatory Roles in Human Keratinocytes under Oxidative Stress as a Receptor for 9-Hydroxyoctadecadienoic Acid

sciencedirect.com/science/articl…

#lcl6

Why is epidermis rich in LA that is unstable and inflammatory under UVB?

How does diet influence lipid composition of skin?

Experience with resistance to sunburns after switching to low n-6 diet is very often, at least in my social bubble. Illustrative story:

yelling-stop.blogspot.com/2010/12/my-vit…

More on G2A and 9-HODE

"The Lipid Receptor G2A (GPR132) Mediates Macrophage Migration in Nerve Injury-Induced Neuropathic Pain"

pubmed.ncbi.nlm.nih.gov/32708184

"Inhibiting the G2A receptor after nerve injury may reduce immune [response] and may thus ameliorate neuropathic pain." 🙈

... and more:

"We discuss the underlying molecular mechanisms of the oxidizedkinokeic acid metabolites and eicosanoids. We evaluate their role as potential targets for the development of novel analgesics..."

Oxidized Lipids in Persistent Pain States

frontiersin.org/articles/10.33…

Note to self (from previous paper): "Linoleic acid is one of the essential ω-6 fatty acids, which leads to formation of the smooth, non-dry outer epidermal barrier upon dietary intake (Hansen et al., 1958; Gill and Valivety, 1997; Nakamura and Nara, 2003; Ramsden et al., 2017)."

It makes sense to me that upstream metabolites of toxic compounds were evolutionary selected as messengers for pain and inflammation.

frontiersin.org/files/Articles…

OXLAMs and psoriasis:

Bioactive Lipid Mediator Profiles in Human Psoriasis Skin and Blood

pubmed.ncbi.nlm.nih.gov/29454560/

All papers in the thread cite the paper from the first tweet.

"Mitochondria are principal destination for labile iron, making these organelles particularly susceptible to oxidative damage on UVA exposure. Labile iron-mediated oxidative damage caused by UVA to mitochondria leads to necrotic cell death via adenosine triphosphate depletion."

https://twitter.com/Ken__Strain/status/1163762064386666496

"Pain Control by Targeting Oxidized Phospholipids: Functions, Mechanisms, Perspectives"

pubmed.ncbi.nlm.nih.gov/33569042

oxPL (cause of harm) = pain

Another connection to pain.

PUFA oxidation sensitivity works probably as local membrane sensor for external insults.

”Are lipid peroxidation processes induced by changes in the cell wall structure and how are these processes connected with diseases?"

sciencedirect.com/science/articl…

"Collectively, these data reveal dietary enrichment with ω-6 PUFAs as a new aetiology of peripheral neuropathy and risk factor for chronic pain and implicate multiple therapeutic considerations for clinical pain management."

https://twitter.com/lipidchronicles/status/1406590204366966785

So we know that breakdown of linoleic acid is mechanistically connected to inflammatory response in sunburns (see the first tweet in the thread ☝️), but does diet influence level of linoleic acid in skin (already asked here

https://twitter.com/martinsipx/status/1358653052257976320

)?

It seems that it does.

https://twitter.com/martinsipx/status/1405697029024763906