CD36

Since DHAP, which you'll recall is a glycolytic intermediate, one of the products from Aldolase, is used as a precursor for ethyl lipid synthesis.

So fatty acids for ethyl lipid synthesis are thought to be derived from fatty acid synthase-mediated de novo lipogenesis, or of course the uptake of fatty acids through, for example, CD36, or hydrolysis of fatty acids from stored tricyclosterol as an oil droplet, and then acyl-CoA utilization to then drive the ethyl lipid production.

Of course, fatty acid synthase, I will mention again, large multifunctional homodimeric enzyme in mammals, primarily synthesizes palmitate, And it is localized portions of the rest of that FAS, which involve elongation of palmitate, are going to be localized in other organelles and not in the cytoplasm, including the peroxisome.

So there's going to be a great deal of interaction between the product of cytosolic fatty acid synthase, generating ultimately acyl-CoAs, and then the utilization of those acyl-CoAs to generate these ether lipids, as well as all of the components of phosphoglycerol lipid and sphingolipid membrane biogenesis, functioning not just with the peroxisome, but also with the endoplasmic reticulum and the Golgi, and the mitochondrion, all membranous.

The main outcome was dilated cardiomyopathy risk.

Being a homozygous CD36 carrier was associated with an odds ratio of 4.8 for dilated cardiomyopathy, while heterozygous carriers had an odds ratio of 1.4. TTN variants carried a higher individual risk with an odds ratio of 8.5, but CD36 contributed more burden at the population level.

CD36 accounted for approximately 9% of dilated cardiomyopathy disease burden, compared with 3.7% for TTN variants.

These findings not only change the current thinking about the genetics of dilated cardiomyopathy in individuals with African ancestry, but they also highlight the importance of representation in genomic research.

Thanks, Chris.

And then from the venous blood, we're also measuring the lipids, um, resting insulin and DNA.

So we're looking at the CD36 gene, which is related to fat transporters in and out of the cell, which has the potential to influence how much you're able to burn.

And then we also collected a urine sample, which will hopefully be used, uh, to detect fructo- fructo- fructose and sucrose in the urine, um, which will hopefully validate the dietary questionnaires.

They then do a few different methods of nutrition analysis.

What did they find? Gimap6 loss resulted in endothelial leak, plus monocyte adhesion was influenced, resulting in accelerated atherosclerosis, myocardial infarction, and heart failure.

Mechanism, increased mitochondrial reactive oxygen species, which in turn affected PPAR gamma, which then influenced CD36, resulting in, uh, differential lipid uptake, which in turn caused foam cells and plaque inflammation.

The human signal, hypomorphic Gimap6 variants, especially V six five, uh, one, were linked to premature coronary artery disease and heart failure without hypercholesterolemia.

Key caution, compelling mechanism, but human, uh, associations need prospective validation before clinical use.