二脒那秦内源性激活血管紧张素转化酶2对细胞脂质沉积的抑制效应及其机制

doi:10.11843/j.issn.0366-6964.2022.08.030

Abstract

Abstract: In this study, 3T3-L1 preadipocytes were induced to transdifferentiate into 3T3-L1 adipocytes to explore the inhibitory effect and mechanism of diminazene aceturate (DIZE) endogenous activation of angiotensin converting enzyme 2 (ACE2) on cell lipid deposition. 3T3-L1 preadipocytes were transdifferentiated. The successfully differentiated 3T3-L1 adipocytes were divided into control group and DIZE group (12.5, 25 μmol·L^-1 treatment), siACE2 group and siACE2 + DIZE group (after siACE2 interference + 25 μmol·L^-1 (dice) for 48 h, supernatant and cells were taken for the following experiments. Results:1) 3T3-L1 adipocytes were successfully induced. Fat droplets appeared in more than 95% of preadipocytes on the 14th day; 2) The action concentrations of DIZE were determined to be 12.5 and 25 μmol·L^-1 When 3T3-L1 adipocytes were treated with the drug concentration and time for 48 hours, the content of triglyceride in cell supernatant decreased significantly (P<0.05) and the content of glucose increased significantly (P<0.05); The lipid droplets of cells in the 25 μmol·L^-1 DIZE treatment group decreased, but the siACE2 group had no significant change. The accumulation of lipid droplets in the siACE2+DIZE group was between the control group and the DIZE group; the ACE2 protein level was significantly higher in the 25 μmol·L^-1 DIZE group. Compared with the control group (P<0.05); the siACE2 group was significantly down-regulated (P<0.05), and the siACE2+DIZE group had no significant change compared with the siACE2 group; 3) Compared with the control group, the expressions of FAS, ACC and SREBP-1c proteins in the 25 μmol·L^-1 DIZE group were down-regulated, while those in the siACE2 group and siACE2+DIZE group were all up-regulated.; 4) Compared with the control group, the expression levels of GLUT4 and CS proteins in the 25 μmol·L^-1 DIZE group were significantly up-regulated (P<0.05), while those in the siACE2 group and siACE2+DIZE group were significantly down-regulated (P<0.05). DIZE treatment improved adipocyte fat deposition by mediating endogenous activation of adipocyte ACE2. Its mechanism:on the one hand, it inhibits lipid synthesis; on the other hand, it promotes glucose uptake and oxidative metabolism, which synergistically reduces fat deposition. The results suggest that ACE2 or DIZE can be used as potential targets or drugs to prevent and control the occurrence and development of fat deposition.

Key words: diminazene aceturate (DIZE), angiotensin converting enzyme 2 (ACE2), lipidosis

CLC Number:

S852.2

CAO Xiyue, FU Yali, XIE Nana, ZHANG Yafeng, ZHANG Yuanshu. Inhibitory Effect and Mechanism of Endogenous Activation of Angiotensin Converting Enzyme 2 by Diminazene Aceturate on Cell Lipid Deposition[J]. Acta Veterinaria et Zootechnica Sinica, 2022, 53(8): 2729-2738.

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Inhibitory Effect and Mechanism of Endogenous Activation of Angiotensin Converting Enzyme 2 by Diminazene Aceturate on Cell Lipid Deposition

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