The study looked at one of the members of the PUFA family that even mainstream medicine is not very fond of. Namely, arachidonic acid (AA). However, the reason medicine is not very fond of that PUFA is due to its role as a precursor to the major inflammatory mediators known as prostaglandins, leukotrienes, and thromboxanes. Medicine does not really have any criticism towards the intact AA or the other members of the PUFA family. Yet, the study below demonstrated that intact AA reliably caused decreased functioning, or even death, of the Sertoli cells (SC) and thus decreased (or even zero) spermatogenesis. The mechanism of action for the those negative effects of AA were purely metabolic – i.e. increased glycolysis and reduced oxygen consumption, paired with lower mitochondrial function. Worse, AA actually reduced the expression of several of the electron chain complexes (ETC), which means its effects were structural (and thus harder to reverse) in additional to functional (lower OXPHOS). Now, while the study was done with SC found in the male gonads, there is nothing SC-specific about the effects of AA. In other words, the same anti-metabolic effects are expected to occur in any type of cell regardless of its origin or maturation state. That automatically makes AA both pro-cancer both for de-novo cancerization and also for growth of already established tumors. It would be great to see a similar study done for other PUFA members, but the available evidence is already pointing in the same direction as the findings about AA below.
https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-024-05182-y
“…As a key factor in determining testis size and sperm number, sertoli cells (SCs) play a crucial role in male infertility. Heat stress (HS) reduces SCs counts, negatively impacting nutrient transport and supply to germ cells, and leading to spermatogenesis failure in humans and animals. However, how HS affects the number of SCs remains unclear. We hypothesized that changes in SC metabolism contribute to the adverse effects of HS. In this study, we first observed an upregulation of arachidonic acid (AA), an unsaturated fatty acid after HS exposure by LC-MS/MS metabolome detection. By increasing ROS levels, expression of KEAP1 and NRF2 proteins as well as LC3 and LAMP2, 100 µM AA induced autophagy in SCs by activating oxidative stress (OS). We observed adverse effects of AA on mitochondria under HS with a decrease of mitochondrial number and an increase of mitochondrial membrane potential (MMP). We also found that AA alternated the oxygen transport and absorption function of mitochondria by increasing glycolysis flux and decreasing oxygen consumption rate as well as the expression of mitochondrial electron transport chain (ETC) proteins Complex I, II, V…”
