Tirzapetide reduces hepatic lipid accumulation by down-regulating the expression of CD36 and OBP2A. (IMAGE)
Caption
(A) Venn analysis of the differentially expressed genes in the livers of mice fed with NCD, HFFC, and HFFC treated with tirzapetide. (B) Clustering analysis was performed on overlapping differentially expressed genes with padjust values less than 0.05. (C) Quantitative PCR was performed to detect the mRNA expression of specific genes (CD36, Cxcl10, Cxcl9, OBP2A, Tgtp1, Ubiquitin D, Aldoc, Dusp1, Socs2) in the livers of mice fed with NCD, HFFC, and HFFC supplemented with tirzapetide. (D) Immunohistochemical staining was performed to detect the protein expression of CD36 and OBP2A in the livers of mice fed with NCD, HFD, HFFC, and HFD or HFFC supplemented with tirzapetide. (E) Western blot analysis of CD36 protein expression in the livers of mice fed with NCD, HFFC, and HFFC supplemented with tirzapetide. (F) siRNAs targeting CD36 or OBP2A (siCD36 or siOBP2A) were transfected into HepG2 cells for 48 h, followed by treatment with 0.2% BSA or 0.2 mM palmitic acid for the last 24 h. Subsequently, the cells were stained with HCS LipidTOX™ Deep Red neutral lipid stain. (G) HepG2 cells were treated for 48 h with 0.2% BSA, 0.2 mM palmitic acid, or palmitic acid combined with 42 nM tirzapetide, with or without transfection of CD36 or OBP2A overexpression plasmids, followed by staining with HCS LipidTOX™ Deep Red neutral lipid stain to assess intracellular lipid accumulation. The average lipid content per cell was quantified using ImageJ software. n = 5 for A–E, n = 3 for F–G. The data are presented as mean ± SD.
Credit
Yun Li, Wencong Sun, Hong Liu, Xiong Z. Ruan
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