NIPSNAP3BはAMPK経路を介してミトコンドリア生合成を亢進させ、小児肥満における脂質蓄積を軽減する

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.

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.

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.

NIPSNAP3B enhances mitochondrial biogenesis to attenuate lipid accumulation via AMPK pathway in CO.