Effects of High-Dose Genistein on the Hypothalamic RNA Profile and Intestinal Health of Female Chicks

Abstract

Genistein is abundant in animal feed. In this study, the side effects of high-dose genistein on intestinal health and hypothalamic RNA profile were evaluated. Chicks exposed to high-dose genistein by intraperitoneal injection (416 ± 21, 34.5 ± 2.5) and feed supplementation (308 ± 19, 27.2 ± 2.1) both showed a reduced body weight gain and feed intake in comparison with the control group (261 ± 16, 22.7 ± 1.6, P < 0.01). In comparison with the control (22.4 ± 0.5, 33.3 ± 2.4), serum levels of albumin and total protein were decreased after high-dose genistein injection (21.6 ± 0.5, 31.8 ± 1.6) and diet supplementation (20.6 ± 0.9, 29.9 ± 2.5, P < 0.001). Interestingly, the genistein diet presented the chick hypothalamus with downregulated expression of bitter receptors (TAS1R3, P < 0.05). Meanwhile, it upregulated the expressions of TAS2R1 (P < 0.05) and downstream genes (PLCB2 and IP3R3) in the ileum (P < 0.05). Accordingly, high-dose dietary genistein reduced villus height and the abundance of Lactobacillus, along with the increased abundance of pathogenic bacteria in the ileum (P < 0.05). Furthermore, transcriptomic analysis identified 348 differently expressed genes (168 upregulated and 224 downregulated) in the high-dose dietary genistein treated group in comparison with the control (P < 0.05, |log2FoldChange| > 0.585). Therefore, high-dose dietary genistein altered the hypothalamic RNA profile and signal processing. Cluster analysis further revealed that high-dose dietary genistein significantly influenced apoptosis, the immune process, and the whole synthesis of steroid hormones in the hypothalamus (P < 0.05). In conclusion, high-dose dietary genistein altered the hypothalamic RNA profile and intestinal health of female chicks.

Genistein Inhibits Proliferation and Metastasis in Human Cervical Cancer Cells through the Focal Adhesion Kinase Signaling Pathway: A Network Pharmacology-Based In Vitro Study in HeLa Cells

“…RNA sequencing was carried out as previously reported [ 62 , 63 ]. Cells were grown with DMSO and genistein (50 μM) for 5 h. Total RNA was isolated using the RNeasy Plus Mini Kit, following the manufacturer’s instructions (Qiagen, Germantown, MD, USA).…”

Dietary daidzein improves the development of intestine subjected to soybean meal in juvenile turbot ( Scophthalmus maximus L.)

“…However, Wang, Jiang, Zhang, Liang, and Yang (2014) found that a dose of 20 mg/kg isoflavones reduced villus length, muscle thickness and villus height/crypt depth ratio (V/C) of the duodenum, jejunum and ileum of chicken. The reduced villus height was also observed in ileum of female chicks fed with a high‐dose of genistein (400 mg/kg) (Lv et al., 2019). It has been reported that the effects of dietary isoflavones on intestinal morphology were in a dose‐dependent manner in broiler chickens (Kamboh & Zhu, 2014).…”

Effects of non‐nutritive sweeteners on growth and intestinal health by regulating hypothalamic RNA profile and ileum microbiota in guinea pigs

“…The arcuate nucleus (ARC) within the hypothalamus plays a crucial role in sensing the body's overall energy status 14 . The ARC contains various neuron groups related to energy homeostasis, including orexin neuropeptide Y (NPY)/agouti‐related peptide (AgRP) neurons and orexin opiomelanocortin (POMC) neurons 15‐17 . The addition of dietary additives such as non‐nutritive sweeteners may influence the production of these appetite‐regulating neuropeptides, potentially altering animal feed intake.…”

“…14 The ARC contains various neuron groups related to energy homeostasis, including orexin neuropeptide Y (NPY)/agoutirelated peptide (AgRP) neurons and orexin opiomelanocortin (POMC) neurons. [15][16][17] The addition of dietary additives such as non-nutritive sweeteners may influence the production of these appetite-regulating neuropeptides, potentially altering animal feed intake. However, the specific effects of non-nutritive sweeteners on the production of ARC-related appetite-related neurons in the hypothalamus remain unknown.…”