Elaidic acid induces hepatic lipid accumulation by inhibiting chaperone-mediated autophagy via the GAS5/miR-27b-3p/SNX10 axis
- Chem Biol Interact. 2026 Jul 25:435:112175. doi: 10.1016/j.cbi.2026.112175.
- 1. College of Food Science and Engineering, Jilin University, Changchun, Jilin, 130062, People's Republic of China.
- 2. College of Food Science and Engineering, Jilin University, Changchun, Jilin, 130062, People's Republic of China; State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun, 130062, People's Republic of China. Electronic address: [email protected].
- 3. College of Food Science and Engineering, Jilin University, Changchun, Jilin, 130062, People's Republic of China. Electronic address: [email protected].
The intake of industrial trans-fatty acids (iTFAs), particularly elaidic acid (EA), has been implicated in non-alcoholic fatty liver disease (NAFLD), yet the underlying mechanisms remain incompletely understood. Functional chaperone-mediated Autophagy (CMA) is essential for maintaining cellular lipid homeostasis. We found that EA exposure reduced the protein level of the CMA rate-limiting component LAMP-2A and induced lipid accumulation in hepatocytes. Importantly, treatment with the CMA activator QX77 significantly alleviated EA-induced lipid accumulation, supporting a functional role for CMA in this process. Cathepsin A (CTSA) is a critical enzyme that promotes the degradation of the LAMP-2A protein. Our data showed that EA upregulated sorting nexin 10 (SNX10), which in turn facilitated CTSA maturation, leading to decreased LAMP-2A abundance. We further investigated the upstream regulatory mechanism of SNX10 from the perspective of competitive endogenous RNA (ceRNA). Bioinformatics analysis and dual-luciferase reporter assays confirmed the existence of the GAS5/miR-27b-3p/SNX10 axis. Long chain non-coding RNA (LncRNA) GAS5 upregulated SNX10 expression by competitively binding to miR-27b-3p. Together, these findings suggested CMA disruption as a possible contributor to EA-induced lipid accumulation and identified the GAS5/miR-27b-3p/SNX10 ceRNA network as a potential regulatory mechanism for CMA.