The Journal of Practical Medicine ›› 2024, Vol. 40 ›› Issue (9): 1197-1203.doi: 10.3969/j.issn.1006-5725.2024.09.004

• Basic Research • Previous Articles     Next Articles

ANGPTL8 knockout reduces lipopolysaccharide⁃induced hepatic lipid deposition

Shan LUO1,2,Ying FENG1,Dandan FAN3,Wenxin ZHENG4,Xingrong GUO1,Xuzhi. RUAN1()   

  1. *.School of Basic Medical Sciences,Hubei University of Medicine,Taihe Hospital,Hubei Key Laboratory of Embryonic Stem Cell Research,Umbilical Cord Blood Hematopoietic Stem Cell Therapy Clinical Medicine Research Center,Shiyan 442000,China
    *.Department of Endocrinology and Rheumatology,Taihe Hospital,Shiyan 442000,China
    Corresponding anthor: RUAN Xuzhi E?mail: 574034343@qq. com
  • Received:2023-10-20 Online:2024-05-10 Published:2024-05-15
  • Contact: Xuzhi. RUAN E-mail:574034343@qq.com

Abstract:

Objective To study the influence of ANGPTL8 in lipopolysaccharide (LPS)?induced hepatic lipid deposition. Methods Male wild?type(WT) and ANGPTL8 knockout mice at 6-8 weeks were used to induce sepsis models by intrabitoneal injection of LPS (10 mg/kg). qPCR and immunofluorescence were used to detected the mRNA and protein expression of ANGPTL8 in liver tissue and HepG2 cells respectively; The contents of alanine aminotransferase (ALT), aspartate aminotransferase (AST) in serum and the triglyceride (TG) and malondialdehyde (MDA) in liver homogenate were detected by kits; the histopathological changes of liver tissue were analyzed through HE staining. Lipids accumulation in liver were detected by oil red O staining. The apoptosis of liver was determinated by TUNEL staining. RNA?seq was used to analyzing the differentially expressed genes in the liver tissue of WT and ANGPTL8 KO mice, and the qPCR and Western Blot were used to verify the differential expressed genes. Results The expression of ANGPTL8 in the liver was significantly upregulated at 48 hours after LPS stimulation. Compared with WT mice, the hepatic lipid deposition, steatosis, and apoptosis were significantly alleviated in liver of ANGPTL8 KO mice, the ALT and AST levels in serum and the TG and MDA content in liver homogenate of ANGPTL8 KO mice were also reduced significantly. The expression of caveolin?1(CAV1) in liver of ANGPTL8 KO mice was significantly higher than that of WT mice. Conclusions LPS promoted the expression and secretion of ANGPTL8 in liver tissue, and ANGPTL8 increased hepatic lipid deposition and peroxidation by inhibiting the expression of CAV1.

Key words: ANGPTL8, LPS, CAV1, lipid deposition, apoptosis

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