FASN is involved in the manufacture of long-chain fatty acids and, alongside cholesterol,
FASN is thought to contribute substrates required for steroidogenesis.
Interestingly we saw no changes in intratumoral FASN gene expression regardless of castration status or diet,
but serum cholesterol levels were strongly predictive of tumor growth and affected very strongly by diet.
The Low Carb diet resulted in lower levels of several important serum cholesteryl esters.
This is likely attributable to the compositional differences between the diets with respect to omega-3 fatty acids.
Interestingly, a difference in free cholesterol only existed for the intact mice on the Low Carb diet,
which had lower levels than the other groups,
including the castrated mice on the Low Carb diet.
The fact that the castrated groups were both high in serum cholesteryl esters (alongside the intact Western diet group) is in accordance with previous literature that reports an increase in cellular cholesteryl esters following castration [24] and [57].
Absence of any further elevation of serum cholesteryl esters in the castrated group fed the Western diet suggests that the capacity of the serum to carry cholesteryl esters may be saturable.
In keeping with this, we observe significant group differences in intratumoral levels of the cholesterol transporter SR-B1.
This ATP binding cassette (ABCA-1) transporter facilitates the cellular uptake and efflux of serum cholesterol,
as mediated both to and from serum high density lipoprotein (HDL) [39] and [58].
This is the major pathway thought to be responsible for enhanced cholesterol uptake into steroidogenic cells, including prostate cancer cells [20].
The Western diet fed intact mice had a lower level of SR-B1,
which was statistically significant as compared with the intact Low Carb diet fed mice or the castrated groups.