Monocyte gene expression in childhood obesity is associated with obesity and complexity of atherosclerosis in adults

Abstract

Childhood obesity coincides with increased numbers of circulating classical CD14++CD16- and intermediate CD14++CD16+ monocytes. Monocytes are key players in the development and exacerbation of atherosclerosis, which prompts the question as to whether the monocytosis in childhood obesity contributes to atherogenesis over the years. Here, we dissected the monocyte gene expression profile in childhood obesity using an Illumina microarray platform on sorted monocytes of 35 obese children and 16 lean controls. Obese children displayed a distinctive monocyte gene expression profile compared to lean controls. Upon validation with quantitative PCR, we studied the association of the top 5 differentially regulated monocyte genes in childhood obesity with obesity and complexity of coronary atherosclerosis (SYNTAX score) in a cohort of 351 adults at risk for ischemic cardiovascular disease. The downregulation of monocyte IMPDH2 and TMEM134 in childhood obesity was also observed in obese adults. Moreover, downregulation of monocyte TMEM134 was associated with a higher SYNTAX atherosclerosis score in adults. In conclusion, childhood obesity entails monocyte gene expression alterations associated with obesity and enhanced complexity of coronary atherosclerosis in adults.

Body fat percentage is more strongly associated with biomarkers of low-grade inflammation than traditional cardiometabolic risk factors in healthy young adults – the Lifestyle, Biomarkers, and Atherosclerosis study

“…CRP and orosomucoid are both independent predictors of future cardiovascular risk [26,27], a relationship consistent with evidence indicating inflammation as a key regulatory process uniting multiple risk factors, including obesity, to the alterations of vascular function seen in atherosclerosis [28]. The detrimental effects of obesity may begin early in life, and childhood obesity is known to be associated with an increased cardiovascular risk in adulthood [29]. Previously, an increase in circulating inflammatory chemokines was found to correlate with preatherosclerotic vascular alterations in young, healthy children [30].…”

Body fat percentage and CRP correlates with a composite score of vascular risk markers in healthy, young adults - The Lifestyle, Biomarkers, and Atherosclerosis (LBA) study

“…However, a wealth of evidence from the 1980's and onwards has indicated inflammation as a main mediator in the progressive endothelial dysfunction that is seen in atherosclerosis [14,61]. Similarly, childhood obesity is linked to an increased cardiovascular risk in adulthood compared to individuals whose obesity started in adulthood [62,63]. Inflammation has been suggested as the key regulatory process linking multiple risk factors, including obesity, to the onset of atherosclerosis [61].…”

Multi-breed genome-wide association studies across countries for electronically recorded behavior traits in local dual-purpose cows

“…The identified potential candidate gene TMEM134 influences obesity and atherosclerosis in adults [59]. Furthermore, TMEM134 is involved in the prototypical inflammatory nuclear factor-κB ( NF-κB ) signaling pathway [59].…”

“…The identified potential candidate gene TMEM134 influences obesity and atherosclerosis in adults [59]. Furthermore, TMEM134 is involved in the prototypical inflammatory nuclear factor-κB ( NF-κB ) signaling pathway [59]. The modulation of downstream NF-κB signaling is the most important characteristic for innate immune programming in chronic inflammation [60].…”