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Although childhood-onset obesity (CO) and adult-onset obesity (AO) are known to lead to distinctive clinical manifestations and disease risks, the fundamental differences between them are largely unclear. The aim of the current study is to investigate the fundamental differences between subcutaneous adipose tissue from CO and AO and identify metabolic differences between abdominal (abSAT) and femoral subcutaneous adipose tissues (feSAT). Total and regional body composition was assessed using DXA and computed tomography. Level of acetyl-CoA, NAD+/NADH, acetyl-CoA network genes, mitochondrial complex abundance, H3 acetylation were determined in biopsied abSAT and feSAT. Serum leptin and adiponectin were measured. Our results showed that acetyl-CoA was higher in subcutaneous adipose tissue from subjects with AO compared to CO. Multiple linear regression revealed that ATP citrate lyase was the only main effect affecting the level of acetyl-CoA. Circulating leptin was higher in AO. The increased level of acetyl-CoA was strongly associated with histone H3 acetylation, LEPTIN expression in adipose tissue and circulating leptin in AO. NAD+/NADH was higher in CO, however, mitochondrial complexes abundance, complex II: complex V and complex IV: complex V ratio were lower in CO, reflecting compromised mitochondrial function in adipose tissue from CO. Moreover, we identified differences in the level of acetyl-CoA and NAD+/NADH ratio between abSAT and feSAT, suggesting that these fat depots may possess different metabolic properties. The fundamental difference in the important metabolic intermediate, acetyl-CoA, between CO and AO may help us better understand the development of obesity and the pathogenesis of different obesity-related diseases in human.

PMID: 32808657 [PubMed - as supplied by publisher]