Synergistic effect of genistein and adiponectin reduces fat deposition in chicken hepatocytes by activating the ERβ-mediated SIRT1-AMPK signaling pathway

Zhihao Jiang; Benzeng Huang; Ziyi Cui; Ze Lu; Haitian Ma

doi:10.1016/j.psj.2024.103734

Synergistic effect of genistein and adiponectin reduces fat deposition in chicken hepatocytes by activating the ERβ-mediated SIRT1-AMPK signaling pathway

Poult Sci. 2024 Apr 5;103(6):103734. doi: 10.1016/j.psj.2024.103734. Online ahead of print.

Authors

Zhihao Jiang¹, Benzeng Huang¹, Ziyi Cui¹, Ze Lu¹, Haitian Ma²

Affiliations

¹ Key Laboratory of Animal Physiology and Biochemistry, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China.
² Key Laboratory of Animal Physiology and Biochemistry, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China. Electronic address: mahaitian@njau.edu.cn.

Abstract

Dietary supplementation with bioactive substances that can regulate lipid metabolism is an effective approach for reducing excessive fat deposition in chickens. Genistein (GEN) has the potential to alleviate fat deposition; however, the underlying mechanism of GEN's fat-reduction action in chickens remains unclear. Therefore, the present study aimed to explore the underlying mechanism of GEN on the reduction of fat deposition from a novel perspective: intercellular transmission of adipokine between adipocytes and hepatocytes. The findings showed that GEN enhanced the secretion of adiponectin (APN) in chicken adipocytes, and the enhancement effect of GEN was completely blocked when the cells were pretreated with inhibitors targeting estrogen receptor β (ERβ) or proliferator-activated receptor γ (PPARγ) signals, respectively. Furthermore, the results demonstrated that both co-treatment with GEN and APN or treatment with the medium supernatant (Med SUP) derived from chicken adipocytes treated with GEN significantly decreased the content of triglyceride and increased the protein levels of ERβ, Sirtuin 1 (SIRT1) and phosphor-AMP-activated protein kinase (p-AMPK) in chicken hepatocytes compared to the cells treated with GEN or APN alone. Moreover, the increase in the protein levels of SIRT1 and p-AMPK induced by GEN and APN co-treatment or Med SUP treatment were blocked in chicken hepatocytes pretreated with the inhibitor of ERβ signals. Importantly, the up-regulatory effect of GEN and APN co-treatment or Med SUP treatment on the protein level of p-AMPK was also blocked in chicken hepatocytes pretreated with a SIRT1 inhibitor; however, the increase in the protein level of SIRT1 induced by GEN and APN co-treatment or Med SUP treatment was not reversed when the hepatocytes were pretreated with an AMPK inhibitor. In conclusion, the present study demonstrated that GEN enhanced APN secretion by activating the ERβ-Erk-PPARγ signaling pathway in chicken adipocytes. Subsequently, adipocyte-derived APN synergized with GEN to activate the ERβ-mediated SIRT1-AMPK signaling pathway in chicken hepatocytes, ultimately reducing fat deposition. These findings provide substantial evidence from a novel perspective, supporting the potential use of GEN as a dietary supplement to prevent excessive fat deposition in poultry.

Keywords: ERβ signal; SIRT1-AMPK signaling pathway; adiponectin; fat-deposition; genistein.