Hormonal
Elevated plasma levels of COL6A3-derived endotrophin, driven by increased body mass index (BMI), causally mediate an increased risk of coronary artery disease (CAD).
This research highlights that high body fat increases a specific protein fragment called endotrophin, which directly contributes to heart disease risk. The good news is that reducing body fat lowers these levels, suggesting that weight management strategies are effective not just for general health, but specifically for mitigating this biological pathway to heart disease.
COL6A3-derived endotrophin mediates the effect of obesity on coronary artery disease: an integrative proteogenomics analysis... COL6A3 was strongly increased by body mass index (BMI)... and increased the risk of CAD... Notably, COL6A3 is cleaved at its C-terminus to produce endotrophin, which was found to mediate this effect on CAD.
Why this rating
The study uses robust Mendelian Randomization (MR) with cis-pQTLs, colocalization, and replication across multiple cohorts (deCODE, UK Biobank, Fenland, ARIC), minimizing confounding and reverse causation, though it is a preprint.
Source
COL6A3-derived endotrophin mediates the effect of obesity on coronary artery disease: an integrative proteogenomics analysis
Satoshi Yoshiji et al. · medRxiv · 2023
DOI 10.1101/2023.04.19.23288706
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