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. 2023 Jan 3:101:skad197.
doi: 10.1093/jas/skad197.

Protective effects of genistein on the production performance and lipid metabolism disorders in laying hens with fatty liver hemorrhagic syndrome by activation of the GPER-AMPK signaling pathways

Longlong Li  1   2 , Yulei Wang  1   2 , Huihui Wang  1   2 , Ying Yang  1   2 , Haitian Ma  1   2
Affiliations

Protective effects of genistein on the production performance and lipid metabolism disorders in laying hens with fatty liver hemorrhagic syndrome by activation of the GPER-AMPK signaling pathways

Longlong Li et al. J Anim Sci. .

Abstract

The aim of this study was to evaluate the beneficial effects and potential mechanisms of genistein (GEN) on production performance impairments and lipid metabolism disorders in laying hens fed a high-energy and low-protein (HELP) diet. A total of 120 Hy-line Brown laying hens were fed with the standard diet and HELP diet supplemented with 0, 50, 100, and 200 mg/kg GEN for 80 d. The results showed that the declines in laying rate (P < 0.01), average egg weight (P < 0.01), and egg yield (P < 0.01), and the increase of the ratio of feed to egg (P < 0.01) induced by HELP diet were markedly improved by 100 and 200 mg/kg of GEN treatment in laying hens (P < 0.05). Moreover, the hepatic steatosis and increases of lipid contents (P < 0.01) in serum and liver caused by HELP diet were significantly alleviated by treatment with 100 and 200 mg/kg of GEN in laying hens (P < 0.05). The liver index and abdominal fat index of laying hens in the HELP group were higher than subjects in the control group (P < 0.01), which were evidently attenuated by dietary 50 to 200 mg/kg of GEN supplementation (P < 0.05). Dietary 100 and 200 mg/kg of GEN supplementation significantly reduced the upregulations of genes related to fatty acid transport and synthesis (P < 0.01) but enhanced the downregulations of genes associated with fatty acid oxidation (P < 0.01) caused by HELP in the liver of laying hens (P < 0.05). Importantly, 100 and 200 mg/kg of GEN supplementation markedly increased G protein-coupled estrogen receptor (GPER) mRNA and protein expression levels and activated the AMP-activated protein kinase (AMPK) signaling pathway in the liver of laying hens fed a HELP diet (P < 0.05). These data indicated that the protective effects of GEN against the decline of production performance and lipid metabolism disorders caused by HELP diet in laying hens may be related to the activation of the GPER-AMPK signaling pathways. These data not only provide compelling evidence for the protective effect of GEN against fatty liver hemorrhagic syndrome in laying hens but also provide the theoretical basis for GEN as an additive to alleviate metabolic disorders in poultry.

Keywords: G protein-coupled estrogen receptor–AMP-activated protein kinase signaling pathways; fatty liver hemorrhagic syndrome; genistein; laying hens; lipid metabolism disorders.

Plain language summary

Fatty liver hemorrhagic syndrome (FLHS) is a nutritional and metabolic disease that seriously threatens the health and performance of laying hens, which is characterized by hepatic steatosis and lipid metabolism disorders. As an isoflavone phytoestrogen, genistein (GEN) exerts many beneficial functions, including alleviating lipid metabolism disorders and anti-inflammatory properties. However, further research is needed on the protective effect and potential mechanism of GEN on the FLHS in laying hens. Here, we found that GEN treatment improved liver injury and decline of production performance in laying hens with FLHS. Moreover, GEN treatment alleviated hepatic steatosis and lipid metabolism disorders through reducing the expression levels of mRNA related to fatty acid transport and synthesis and enhancing the mRNA expression levels of factors associated with fatty acid oxidation in FLHS layers, which may be achieved by activation of the G protein-coupled estrogen receptor–adenosine 5'-monophosphate (AMP)-activated protein kinase signaling pathways. These data not only provide compelling evidence for the protective effects and mechanisms of GEN against FLHS in laying hens but also provide the theoretical basis for GEN to alleviate other metabolic disorders in poultry.

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Conflict of interest statement

The authors declare that there are no competing interests associated with this study.

Figures

Figure 1.
Figure 1.
Effects of genistein (GEN) on the production performance in HELP-induced laying hens. (A) Laying rate; (B) average egg weight; (C) daily feed intake; (D) egg yield; (E) ratio of feed to egg. Data are expressed as mean ± SE (n = 5 to 8). ##P < 0.01 compared to the control group; *P < 0.05 and **P < 0.01 compared to the high-energy and low-protein (HELP) group.
Figure 2.
Figure 2.
Effects of genistein (GEN) on the histopathology observation in the liver of laying hens fed a high-energy and low-protein (HELP) diet. (A) Hepatic morphology observation; (B) H&E staining; (C) Oil Red O staining. n = 3. Scale bars, 50 μm.
Figure 3.
Figure 3.
Effects of genistein (GEN) on the liver index and abdominal fat index in HELP-induced laying hens. (A) Liver index; (B) abdominal fat index. Data are expressed as mean ± SE (n = 19 to 21). ##P < 0.01 compared to the control group; *P < 0.05 and **P < 0.01 compared to the high-energy and low-protein (HELP) group.
Figure 4.
Figure 4.
Effects of genistein (GEN) on the liver function in laying hens fed a high-energy and low-protein (HELP) diet. (A) Serum albumin (ALB) content; (B) serum total protein (TP) content. Data are expressed as mean ± SE (n = 8). ##P < 0.01 compared to the control group; *P < 0.05 and **P < 0.01 compared to the HELP group.
Figure 5.
Figure 5.
Effects of genistein (GEN) on the serum lipid levels in HELP-induced layers. (A) Serum triglyceride (TG) content; (B) serum total cholesterol (TC) content; (C) serum low-density lipoprotein cholesterol (LDL-C) content; (D) serum high-density lipoprotein cholesterol (HDL-C) content; (E) serum lipoprotein lipase (LPL) activity. Data are expressed as mean ± SE (n = 8 to 12). ##P < 0.01 compared to the control group; *P < 0.05 and **P < 0.01 compared to the high-energy and low-protein (HELP) group.
Figure 6.
Figure 6.
Effects of genistein (GEN) on the lipid accumulation in the liver of laying hens fed a high-energy and low-protein (HELP) diet. (A) Hepatic triglyceride (TG) content; (B) hepatic total cholesterol (TC) content; (C) hepatic nonesterified fatty acids (NEFA) content; (D) hepatic hepatic lipase (HL) activity. Data are expressed as mean ± SE (n = 12). ##P < 0.01 compared to the control group; *P < 0.05 and **P < 0.01 compared to the HELP group.
Figure 7.
Figure 7.
Effects of genistein (GEN) on the mRNA expression levels of lipid metabolism-related factors in HELP-stimulated laying hens. (A) Relative apolipoprotein B (APOB) mRNA level; (B) relative platelet glycoprotein 4 (CD36) mRNA level; (C) relative acetyl-CoA carboxylase α (ACCα) mRNA level; (D) relative ATP-citrate lyase (ACLY) mRNA level; (E) relative fatty acid synthase (FASN) mRNA level; (F) relative sterol regulatory element binding protein 1c (SREBP-1c) mRNA level; (G) relative carnitine palmitoyltransferase 1 (CPT-1) mRNA level; (H) relative adipose triglyceride lipase (ATGL) mRNA level. Data are expressed as mean ± SE (n = 6 to 8). ##P < 0.01 compared to the control group; *P < 0.05 and **P < 0.01 compared to the high-energy and low-protein (HELP) group.
Figure 8.
Figure 8.
Effects of genistein (GEN) on the expression of factors related to GPER–AMPK pathways in laying hens fed a HELP diet. (A) Relative G protein-coupled estrogen receptor (GPER) mRNA level; (B) immunoblot of GPER (left), and the right panel shows semiquantitative analysis of the immunoblotting results; (C) immunoblot of AMP-activated protein kinase (AMPKα), p-AMPKα, acetyl-CoA carboxylase α (ACCα), and p-ACCα (left), and the right panel shows semiquantitative analysis of the immunoblotting results. Data are expressed as mean ± SE (n = 4). ##P < 0.01 compared to the control group; *P < 0.05 and **P < 0.01 compared to the high-energy and low-protein (HELP) group.
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