Knockout of Stearoyl-CoA Desaturase 1 Decreased Milk Fat and Unsaturated Fatty Acid Contents of the Goat Model Generated by CRISPR/Cas9

Tian, Hui; Niu, Huimin; Luo, Jun; Yao, Weiwei; Chen, Xiaoying; Wu, Jiao; Geng, Yanan; Gao, Wenchang; Lei, Anmin; Gao, Zhimin; Tian, Xiue; Zhao, Xiaoe; Shi, Huaiping; Liu, Cong; Hua, Jinlian

doi:10.1021/acs.jafc.2c00642

Cited by 11 publications

(4 citation statements)

References 71 publications

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“…NaAc ( Figures 1C , D ), sodium propionate ( Figures 1F , G ), but not sodium butyrate ( Figures 1I , J ) significantly increased the phosphorylation level of ERK at the concentration of 0.75 mM ( p < 0.05). Previously study found GPCR-regulated cellular cAMP involved in the modification of mTORC1 activity, which is a crucial pathway for milk synthesis ( 26 ). Activation of G αi protein could inhibit AC (adenylate cyclase) from converting ATP into cAMP, then inhibit the phosphorylation of CREB.…”

Section: Resultsmentioning

confidence: 99%

Sodium acetate regulates milk fat synthesis through the activation of GPR41/GPR43 signaling pathway

Zheng²,

Liu³

et al. 2023

Front. Nutr.

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BackgroundFat is a critical component in milk, which provided energy for the early growth and development of mammals. Milk fat is positively related to the concentration of acetate in the blood, while the underlying mechanism is still unclear.ObjectiveThis study is to investigate the effects of sodium acetate (NaAc) on milk fat synthesis in the mammary gland, and explored the underlying mechanism.MethodsIn vitro experiments were carried out in mouse mammary epithelial cell line (HC11) cells cultured with NaAc to explore the potential pathway of NaAc on milk fat synthesis. Furthermore, 24 pregnant mice (from d 18.5 of gestation to d 7 of lactation, exposed to 200 mM NaAc drinking water) were used as an in vivo model to verify the results.ResultsIn this study, we found that NaAc promoted milk fat synthesis and the expression of related genes and proteins in HC11 mammary epithelial cells with the activation of GPCR and mTORC1 signaling pathways (p < 0.05). Pretreatment with the mTORC1 inhibitors and G protein inhibitors attenuated the NaAc-induced milk fat synthesis in HC11 mammary epithelial cells (p < 0.05). Importantly, the effect of NaAc on milk synthesis was attenuated in GPR41 and GPR43 knockdown HC11 mammary epithelial cells (p < 0.05). This evidence indicates that NaAc might regulate milk fat synthesis through the GPR41/GPR43-mTORC1 pathway. Consistently, in in vivo experiment, dietary supplementation with NaAc significantly increased milk fat content and fat synthesis-related proteins in mice mammary glands with the activation of mTORC1 and GPCR signaling pathways at peak lactation (p < 0.05).ConclusionThe addition of NaAc promoted the increase of milk fat synthesis in HC11 mammary epithelial cells and mice mammary glands at peak lactation. Mechanistically, NaAc activates GPR41 and GPR43 receptors, leading to the activation of the mTORC1 signaling pathway to promote the synthesis of milk fat.

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Section: Resultsmentioning

confidence: 99%

Sodium acetate regulates milk fat synthesis through the activation of GPR41/GPR43 signaling pathway

Zheng²,

Liu³

et al. 2023

Front. Nutr.

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“…Even when the diet was supplemented with high levels of MUFA, decreasing SCD activity seemingly decreased lipid accumulation by limiting the supply of endogenously synthesized MUFAs [ 43 ]. There is ample evidence indicating that SCD can influence the partitioning of fatty acids into and out of neutral lipid species, which is essential in lipid metabolism and body weight control [ 44 , 45 ]. SCD is emerging as a potential therapeutic target for treating obesity, diabetes, and other metabolic diseases [ 46 , 47 ].…”

Section: Discussionmentioning

confidence: 99%

Mechanism of SCD Participation in Lipid Droplet-Mediated Steroidogenesis in Goose Granulosa Cells

Yuan

Abdul-Rahman

et al. 2022

Genes

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Stearoyl-CoA desaturase (SCD) is a key enzyme catalyzing the rate-limiting step in monounsaturated fatty acids (MUFAs) production. There may be a mechanism by which SCD is involved in lipid metabolism, which is assumed to be essential for goose follicular development. For this reason, a cellular model of SCD function in goose granulosa cells (GCs) via SCD overexpression and knockdown was used to determine the role of SCD in GC proliferation using flow cytometry. We found that SCD overexpression induced and SCD knockdown inhibited GCs proliferation. Furthermore, ELISA analysis showed that SCD overexpression increased the total cholesterol (TC), progesterone, and estrogen levels in GCs, while SCD knockdown decreased TC, progesterone, and estrogen levels (p < 0.05). Combining these results with those of related multi-omics reports, we proposed a mechanism of SCD regulating the key lipids and differentially expressed gene (DEGs) in glycerophospholipid and glycerolipid metabolism, which participate in steroidogenesis mediated by the lipid droplet deposition in goose GCs. These results add further insights into understanding the lipid metabolism mechanism of goose GCs.

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“…Furthermore, the gene expression of SCD1 was upregulated in the peak lactation period, which was due to its function as a key enzyme in the synthesis of milk fat in mammary glands [ 4 ]. In SCD1-knockout goats, the milk fat percentage was reduced [ 29 ]. As expected, we found that the expression of ACCα, FAS, and SCD1 was upregulated with the addition of acetate.…”

Section: Discussionmentioning

confidence: 99%

Acetate-Induced Milk Fat Synthesis Is Associated with Activation of the mTOR Signaling Pathway in Bovine Mammary Epithelial Cells

Jiang

Yang

et al. 2022

Animals

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Acetate is a precursor substance for fatty acid synthesis in bovine mammary epithelial cells (BMECs), and the mTOR signaling pathway plays an important role in milk fat synthesis. However, the mechanism of the regulatory effects of acetate on lipogenic genes via the mTOR signaling pathway in BMEC remains unknown. We hypothesized that acetate can enhance the expression of lipogenic genes and triglyceride (TG) production by activating the mTOR signaling pathway in BMECs. Therefore, the aim of this study was to investigate the network of acetate-regulated lipid metabolism by the mTOR signaling pathway in BMECs. These results showed that TG synthesis was elevated (p < 0.01) in BMECs with acetate treatment. The lipid droplets were increased in the acetate-treated groups compared with those in the control group through the Bodipy staining of the lipids. In addition, the fatty acid profile in BMECs treated with acetate was affected, with an elevation in the proportions of C14:0, C16:0, and C18:0. The mRNA levels of the sterol-response-element-binding protein 1 (SREBP1), stearoyl-CoA desaturase 1 (SCD1), and fatty acid synthase (FAS) genes involved in the lipogenesis and transcriptional factors were upregulated (p < 0.05) in BMECs with acetate treatment. Remarkably, the expression of acetyl-CoA carboxylase α (ACCα) and FAS rate-limiting enzymes involved in lipogenesis was upregulated in BMECs with acetate treatment. Moreover, the addition of acetate enhanced the key protein expression of S6K1, which is related to the mTOR signaling pathway. Taken together, our data suggest that TG accumulation and expression of lipogenic genes induced by acetate are associated with the activation of the mTOR signaling pathway, which provides new insights into the understanding of the molecular mechanism in the expression of mTOR-signaling-pathway-regulated lipogenic genes.

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Knockout of Stearoyl-CoA Desaturase 1 Decreased Milk Fat and Unsaturated Fatty Acid Contents of the Goat Model Generated by CRISPR/Cas9

Cited by 11 publications

References 71 publications

Sodium acetate regulates milk fat synthesis through the activation of GPR41/GPR43 signaling pathway

Sodium acetate regulates milk fat synthesis through the activation of GPR41/GPR43 signaling pathway

Mechanism of SCD Participation in Lipid Droplet-Mediated Steroidogenesis in Goose Granulosa Cells

Acetate-Induced Milk Fat Synthesis Is Associated with Activation of the mTOR Signaling Pathway in Bovine Mammary Epithelial Cells

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