NIPSNAP3B elevates mitochondrial biogenesis to attenuate lipid accumulation in childhood obesity via AMPK pathway

OBJECTIVE: Childhood obesity (CO) has become a global epidemic, leading to rising burden of many diseases and premature death. Thus, this study was conducted to screen the mitochondria-associated biomarkers for patients with CO, as well as the involved molecular mechanism. METHODS: After downloading GSE29718 and GSE104815 datasets from GEO database, differential expression analysis was conducted to screen the DEGs. Then the obtained DEGs were intersected with the mitochondrial-associated genes, and mitochondrial-related genes in CO were acquired, followed by key mitochondrial-related genes screening utilizing three machine learning algorithms. The qRT-PCR and western blot were employed to determine the expression of key genes. Gain-of-function experiment was applied to investigate the function of NIPSNAP3B in CO in vitro. RESULTS: Total 364 DEGs were screened, then 18 mitochondrial-related genes in CO were obtained. These 18 mitochondrial-associated genes in CO enriched in pyruvate metabolism, arginine biosynthesis, and AMPK signaling pathway, etc. ACACB and NIPSNAP3B were considered as the key mitochondrial-related genes. Of note, NIPSNAP3B overexpression markedly reduced the TG level and the protein expression levels of PPARγ and C/EBPα in MDI-induced 3 T3-L1 cells. Also, ATP content, mitochondrial mass, MMP, and protein expression levels of PGC-1α, NRF1, and TFAM were changed after NIPSNAP3B upregulation in MDI-induced 3 T3-L1 cells. However, opposite results were observed after NIPSNAP3B downregulation. Compound C (AMPK inhibitor) or AMPK knockdown administration could reverse the effect of NIPSNAP3B on adipocyte lipid deposition and mitochondrial biogenesis. CONCLUSION: NIPSNAP3B enhances mitochondrial biogenesis to attenuate lipid accumulation via AMPK pathway in CO.