Fig 2: Liraglutide activates TFEB and its downstream targets through GLP-1R. (A) Western blot analysis of GLP-1R protein levels in the liver of HFD-fed mice treated with or without liraglutide. Relative expression levels were normalized to β-actin levels. (B,C) Western blot detection of GLP-1R in primary mouse hepatocytes and HepG2 cells treated with or without liraglutide. (D) Western blot detection of GLP-1R, TFEB, and its downstream targets CTSB and LAMP1 in HepG2 cells transfected with TFEB-siRNA or control-siRNA. (E) Western blot detection of GLP-1R, TFEB, and its downstream targets CTSB and LAMP1 in HepG2 cells with or without GLP-1R overexpression. The data are expressed as the mean ± SEM; n = 3. *P < 0.01, **P < 0.05 vs. Chow + saline group or BSA group or siCON + PA group or Vector-PA group; #P < 0.01, ##P < 0.05 vs. HFD + saline group or PA group or siCON + PA group or Vector-PA group; &P < 0.01, &&P < 0.05 vs. siCON + PA + LG group or Vector-PA + LG group.

Fig 3: Dysregulation of lipid metabolism by CTSB overexpression in 3T3L1 adipocytes. (A and B) Lipid droplets (LDs) were stained by Nile red in Mock or CTSB-OE 3T3L1 adipocytes. Representative images (A) and quantitative data of the mean LD diameter (B) are shown. Scale bar represents 50 μm. Values indicate the mean ± SD. Differences between values were analysed by Student’s t-test with *P < 0.05, **P < 0.01. (C and D) Release assays for glycerol (C) and measurement of intracellular TG content (D) were performed in Mock or CTSB-OE 3T3L1 adipocytes. Values indicate the mean ± SD. Differences between values were analysed by Tukey-Kramer method with *P < 0.05, **P < 0.01.

Fig 4: Taurine inhibited the elevated levels of autophagy, NLRP3 inflammasome activation, and the release of LDH caused by As2O3.a The effect of Tau on the expression of LC3, p62, CTSB, NLRP3, caspase-1 p20, and IL-1β p17 in As2O3-treated HepG2 cells, and densitometric analyses of LC3, p62, CTSB, NLRP3, caspase-1 p20, and IL-1β. b Effects of As2O3 and Tau on LDH release rate in HepG2 cells. Values are mean ± SD, and n = 3. *P < 0.05 compared with the control group, #P < 0.05 compared with the As2O3 group

Fig 5: Effects of Tau on CTSB levels, pyroptosis, and lipid accumulation.a Detection of cytosolic lysosomal and CTSB Levels after As2O3 and Tau Treatments. b Effects of Tau on As2O3-induced double-positivity for PI and activated caspase-1 staining. c Effects of Tau on the As2O3-induced accumulation of lipids. Values are mean ± SD, and n = 3. *P < 0.05 compared with the control group, #P < 0.05 compared with the As2O3 group; Scale bar = 50 μm