The Lipid Droplet-Associated Hydrolase Is Associated With Obesity and Adipose Tissue Inflammation in Children.

Abstract

The lipid droplet-associated hydrolase (LDAH) is a lipid droplet-associated protein with an uncharacterized role in human adipose tissue (AT) and obesity; we aimed to investigate its role in human AT and its relevance for childhood obesity. LDAH variant rs13385191 and gene expression were analyzed in a cross-sectional study of subcutaneous AT samples from 296 children (120 girls, 176 boys; ages 0-18; BMI SDS -2.7 to 4.3), and an association with obesity and AT biology was studied. An effect of LDAH on adipogenesis was investigated in SGBS preadipocytes. Minor allele carriers of rs13385191 showed lower AT LDAH expression compared to non-carriers (p < 0.001) and a trend toward higher BMI SDS, which was, however, not statistically significant (p = 0.062). Consistently, study participants with lower LDAH expression showed higher BMI SDS (p = 0.005). A negative correlation was found between LDAH and macrophage infiltration into AT after controlling for age (R = -0.132; p = 0.039), and high LDAH expression was associated with lower circulating TNFα (p = 0.017). LDAH expression increased during SGBS adipocyte differentiation, while its knockdown did not alter differentiation. In line with results from AT, TNFα significantly reduced LDAH expression in SGBS cells (p = 0.009). LDAH seems to have a role in AT inflammation and the development of obesity in children.