Overexpression of salusin‑α upregulates AdipoR2 and activates the PPARα/ApoA5/SREBP‑1c pathway to inhibit lipid synthesis in HepG2 cells

Zhang,Huan; Yang,Chao; Wang,Songjiao; Xu,Aohong; Zhang,Qian; Duan,Xiuqun; Gong,Guofu; Wang,Yuxue

doi:10.3892/ijmm.2023.5244

Overexpression of salusin‑α upregulates AdipoR2 and activates the PPARα/ApoA5/SREBP‑1c pathway to inhibit lipid synthesis in HepG2 cells

Authors:
- Huan Zhang
- Chao Yang
- Songjiao Wang
- Aohong Xu
- Qian Zhang
- Xiuqun Duan
- Guofu Gong
- Yuxue Wang
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Affiliations: Department of Laboratory Medicine, Hubei University of Chinese Medicine, Wuhan, Hubei 430065, P.R. China, Department of Clinical Laboratory, Ezhou Central Hospital, Ezhou, Hubei 436000, P.R. China, Department of Emergency, Xiangyang Central Hospital, Xiangyang, Hubei 441032, P.R. China
Published online on: April 6, 2023 https://doi.org/10.3892/ijmm.2023.5244
Article Number: 41
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Salusin‑α and adiponectin, are vasoactive peptides with numerous similar biological effects related to lipid metabolism. Adiponectin has been shown to reduce fatty acid oxidation and to inhibit lipid synthesis of liver cells through its receptor, adiponectin receptor 2 (AdipoR2), but whether salusin‑α is able to interact with AdipoR2, was not previously reported. To investigate this, in vitro experiments were carried out. The overexpression and interference recombinant plasmids were constructed with salusin‑α. The lentiviral expression systems of salusin‑α overexpression and interference were respectively synthesized in 293T cells, and 293T cells were infected with the lentivirus. Finally, the association between salusin‑α and AdipoR2 was analyzed by semi‑quantitative PCR. Subsequently, HepG2 cells were also infected with these viruses. The expression levels of AdipoR2, peroxisome proliferator‑activated receptor‑α (PPARα), apolipoprotein A5 (ApoA5) and sterol regulatory element‑binding transcription factor 1 (SREBP‑1c) were detected by western blotting, and AdipoR2 inhibitor (thapsigargin) and agonist [4‑phenyl butyric acid (PBA)] were used to observe the resultant changes in the aforementioned molecules. The results obtained revealed that the overexpression of salusin‑α increased the level of AdipoR2 in 293T and HepG2 cells, led to an upregulation of the levels of PPARα and ApoA5, and inhibited the expression of SREBP‑1c, whereas the salusin‑α interference lentivirus exerted the opposite effects. Notably, thapsigargin inhibited the expression of AdipoR2, PPARα and ApoA5 in HepG2 cells of pHAGE‑Salusin‑α group, and caused an increase in the level of SREBP‑1c, whereas the opposite effects were observed in pLKO.1‑shSalusin‑α#1 group upon treatment with PBA. Taken together, these data demonstrated that overexpression of salusin‑α upregulated AdipoR2, which in turn activated the PPARα/ApoA5/SREBP‑1c signaling pathway to inhibit lipid synthesis in HepG2 cells, thereby providing theoretical data on which to base the clinical application of salusin‑α as a novel peptide for molecular intervention in fatty liver disease.

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