George posted the link to this editorial in the comments of a post some considerable time ago (so it seems now). So this is another old post which has been lying around on the hard drive... Anyway the link is:
Making sense of a seemingly odd connection
It gives an overview and extension of the ideas included in a paper in the same edition of the European Heart Journal
TRAK2, a novel regulator of ABCA1 expression, cholesterol efflux and HDL biogenesis
Both papers are steeped, very deeply, in the Lipid Hypothesis. As such, the chances of them doing anything useful for anyone at all are vanishingly small. Because TRAK2 reduces HDL formation and knocking it down increases HDL, the obvious conclusion is:
"TRAK2 may therefore be an important target in the development of anti-atherosclerotic therapies"
Another target to raise HDL... Sigh, here we go again.
You have to understand that, in the 1950s, the Lipid Hypothesis was bollocks. At no point has anything ever been found to alter that situation. As such I find it very hard to worry about ApoB counts, ApoB sizes, oxidised LDL etc etc etc. including low HDL. Manipulating these numbers by sugar avoidance and saturated fat inclusion will do good. Manipulating them with drugs will bomb. We all still giggle over torcetrapib, anacetrapib, any-other-etrapib and their astronomical, yet useless, levels of HDL.
However, there is that one simple intervention which raises HDL in an effective and totally non toxic manner.
That is saturated fat. Monounsaturated fat is neutral and omega six PUFA lowers HDL. The editorial points out, very perceptively, that not only is 27-hydroxycholesterol a key messenger in HDL formation, but that HDL can be viewed as an export mechanism for free radicals.
Saturated fat raises HDL. Saturated fat drives FADH2 facilcitated RET through complex I in the mitochondria. This process is, undoubtedly, beneficial. Is it the RET which drives the HDL formation? Whether the rise in HDL itself is of benefit or whether the benefits accrue solely from the RET, generated by palmitic acid, which facilitated its formation is an interesting area to speculate in.
MUFA are less effective at RET and HDL generation than saturates. PUFA are useless at both RET and (subsequent?) HDL formation.
HDL, as a vehicle for ROS modified sterols, might be good for you per se. Raising HDL without the ROS/oxidised sterols will be useless. Forget TRAK2.
Just my two penneth.