Overexpression CPT1A reduces lipid accumulation via PPARα/CD36 axis to suppress the cell proliferation in ccRCC

Clear cell renal carcinoma (ccRCC) is histologically defined by its cytoplasmic lipid deposits. Lipid metabolism disorder largely increases the risk of ccRCC. In this study, we aimed to investigate the biological functions and molecular mechanisms of carnitine palmitoyl transferase 1A (CPT1A) in ccRCC. Our results showed that CPT1A is decreased in ccRCC clinical samples and cell lines compared with that in normal samples. Lentivirus overexpressing CPT1A was used to investigate the neoplastic phenotypes of ccRCC, and the results showed that lipid accumulation and tumor growth are attenuated both in vitro and in vivo. In addition, CPT1A prevents cholesterol uptake and lipid accumulation by increasing the peroxisome proliferator-activated receptor alpha (PPAR alpha) level through regulation of Class B scavenger receptor type 1 (SRB1) and cluster of differentiation 36 (CD36). Furthermore, PI3K/Akt signaling pathway promotes tumor cell proliferation in ccRCC, which is related to the enhanced expression of CD36. Functionally, weakened CPT1A expression is critical for lipid accumulation to promote ccRCC development. Collectively, our research unveiled a novel function of CPT1A in lipid metabolism via PPAR alpha/CD36 axis, which provides a new theoretical explanation for the pathogenesis of ccRCC. Targeting CPT1A may be a potential therapeutic strategy to treat ccRCC.

Automated summary

In this study, we investigated the biological functions and molecular mechanisms of CPT1A in ccRCC. Our results showed that CPT1A is decreased in ccRCC samples and cell lines. Overexpression of CPT1A attenuated lipid accumulation and tumor growth in vitro and in vivo. CPT1A prevented cholesterol uptake and lipid accumulation through regulation of PPAR alpha, SRB1, and CD36. The PI3K/Akt signaling pathway promoted tumor cell proliferation in ccRCC, which was associated with enhanced expression of CD36. Our study revealed a novel function of CPT1A in lipid metabolism via the PPAR alpha/CD36 axis and provided a new theoretical explanation for the pathogenesis of ccRCC.