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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: LDAH seems to have a role in AT inflammation and the development of obesity in children.