Ceramides and de Novo Lipogenesis
Interestingly enough I’ve been pondering the development of atherogenesis and dyslipidemia a bunch. The pathology of vascular disease is a part of my job, but there is so much unknown about how humans develop atherosclerosis and dyslipidemia and what factors really cause cardiovascular disease. It’s mind-boggling how ignorant we are on the subject yet pretend to know all of the answers. But such is the historical trend in nutritional and physiological related sciences — publish an idea and insist that that idea is the end all, be all of a controversy. That is, until it’s disproven. For examples of this, see the lipid hypothesis and the saturated fat hypothesis (there are lots of others like these).
So what about ceramides?
Ceramides are lipid molecules produced by the body primarily from palmitate (they can come from other products as well), which just so happens to be the major fatty acid produced from de novo lipogenesis (DNL) in humans. Ceramides have different functions in the body, both in terms of proper cellular function and the pathogenesis of chronic disease (as shown above), but for this topic of discussion I want to discuss their role in the development of CVD. In particular, ceramides are becoming increasingly known for their role in the development of CVD and as a stronger predictor of mortality than LDL concentration. It may also be the reason why statins don’t seem to work all that well in preventing mortality, even though they do their intended job — lowering LDL levels. It could be argued that the increase in LDL levels may just be a coincidence, and there is some very interesting physiology that may prove this point to be the case.
The bridge in the literature: NAFLD
Non-Alcoholic Fatty Liver Disease is a very interesting condition, IMO. Until recently, fatty liver disease was primarily seen in alcoholics due to the over-consumption of alcohol. Now, fatty livers are much more attributed to overnutrition and physical activity. Interestingly, a person can have NAFLD without being obese themselves, though many of these individuals are obese.
NAFLD is associated with a higher risk of a ton of diseases, and seems to be a comorbidity in almost every chronic disease I can think of — especially CVD and diabetes. The interesting thing to note about NAFLD is that individuals with NAFLD seem to have higher rates of DNL than healthy individuals.
And a lot of the pathogenesis and the increased DNL seems to be the result of an excess of fructose consumption.
Excess fructose has also been shown to increase the levels of VLDL and LDL (“bad” cholesterol), which are two huge conventional risk factors for the development of CVD, dyslipidemia, and other conditions.
So remember the first part of this article where I mention that the main product of DNL is palmitic acid, and that palmitic acid is a main contributor to the development of ceramide accumulation?
If fructose consumption in the diet contributes to increased DNL and the accumulation of palmitic acid, it could also be the case that there would be an increase amount of ceramides in the blood, thereby inducing CVD. The increased output of VLDL and LDL may just be a coincidence with the increased ceramide production, and the attempts to associate CVD and LDL may have just been a wild goose chase all along.