Mechanisms explaining the relationship between
obesity and
cardiovascular disease (CVD) are needed. Despite growing recognition of the importance of the anucleate platelet transcriptome, low levels of
RNA in platelets make assessment difficult. We sought to perform unbiased platelet
RNA profiling in
obesity by performing a prospective study of
severe obesity and
weight loss via
bariatric surgery on platelet characteristics and
mRNA profile in 26 pre-menopausal, non-diabetic women (31.6 ± 8.4 years; BMI 43.0 ± 6.5 kg/m2) who underwent sleeve
gastrectomy. Totally, 10 women of similar age with normal BMI served as controls. Platelet activation via flow cytometry was assessed before and after surgery.
RNA-sequencing (RNAseq) was performed on platelet isolates from a subset of 13 subjects (eight obese women and five normal-BMI subjects). Platelet count, size, and age did not differ between control and obese women. However, platelet surface
P-selectin and CD40 were higher in
obesity. RNAseq demonstrated 629 differentially abundant transcripts in
obesity. Notably, S100A9 and AGER, established markers of cardiovascular risk, were two of the most highly upregulated transcripts (each > 2.5 fold). At 6 months post-operatively, subjects lost 26.1 ± 5.8%
body weight and inducible platelet
P-selectin expression was reduced. Expression of 170 transcripts was affected by surgery, but only a small fraction (46/629) were genes found altered in
obesity. We demonstrate that
obesity is associated with an altered platelet transcriptome and increased platelet activation, which is partly attenuated by
bariatric surgery. These observations suggest that platelets may contribute to increased cardiovascular risk in
obesity through a variety of mechanisms.