Soybean isoflavone promotes milk yield and milk fat yield through the ERα-mediated Akt/mTOR pathway in dairy goats

Soybean isoflavone (SIF) in soybeans are natural phytoestrogens, which is functioned as an estrogen agonistic or antagonistic. SIF regulates the capacity of animals to synthesize triacylglycerols by directly utilizing long-chain fatty acids. However, few studies have focused on its regulatory lipid metabolism in lactating dairy goats. The objective of this study was to investigate the influence of SIF on milk yield and composition using Saanen dairy goats as a model, employing both in vivo and in vitro approaches. In the in vivo phase, a total of 20 goats were randomly divided into 2 groups: the control group fed a basal diet, and the experimental group fed a basal diet supplemented with SIF at a dosage of 100 mg/d. The results underscored a significant elevation in serum estrogen and prolactin levels in the SIF-supplemented group (P < 0.05). Notably, SIF supplementation also displayed a higher milk fat percentage (P = 0.03). Transitioning to in vitro experimentation, the addition of SIF (75 <mu>M) to goat mammary epithelial cells exhibited a pronounced effect on cell proliferation. It spurred cell proliferation and led to an increase in triacylglycerol levels (P < 0.05). Consistently, SIF showcased an enhancement in the expression of key genes associated with milk fat de novo synthesis. SIF demonstrated a rescuing effect on the suppressive impact of MK2206 on Akt protein phosphorylation. Importantly, the study observed that the knockdown of estrogen receptor alpha (ER alpha) expression completely counteracted the effect of SIF on lipid droplet accumulation. Collectively, the current study establishes the critical role of SIF in process of fatty acid de novo in the goat mammary gland. This regulation is notably mediated through the ER alpha-Akt axis, thus enriching our understanding of this intricate biological process. This research sheds light on the potential benefits of SIF supplementation in dairy goat farming, ultimately contributing to improved milk production and quality. Lay Summary This study aimed to assess the impact of soybean isoflavone (SIF) on milk production and composition in dairy goats. In vivo experiments revealed that SIF supplementation (100 mg/d) significantly raised serum estrogen and prolactin levels, resulting in increased milk yield and fat content compared to the control group. In vitro analysis demonstrated that SIF (75 mu M) promoted cell proliferation and triacylglycerol synthesis in goat mammary epithelial cells. It also upregulated genes related to milk fat synthesis, such as FAS N, SREBP1c, ACACA, and ACSS2. Notably, SIF mitigated the suppressive effect of MK2206 on Akt protein phosphorylation and its effects on lipid droplet accumulation were abrogated by estrogen receptor alpha (ER alpha) knockdown. This research underscores that SIF plays a crucial role in process of fatty acid de novo in goat mam-mary glands, mediated via the ER alpha-Akt axis, highlighting its potential benefits in dairy goat farming for improved milk production and quality.