β-Hydroxybutyrate Facilitates Fatty Acids Synthesis Mediated by Sterol Regulatory Element-Binding Protein1 in Bovine Mammary Epithelial Cells

Zhang, Min; Zhang, Shiqi; Qi, Hui; Lei, Lin; Du, Xiliang; Gao, Wenwen; Zhang, Renhe; Li, Xiaobing; Li, Xinwei

doi:10.1159/000438569

Cited by 32 publications

(27 citation statements)

References 30 publications

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“…Work in nonruminants has indicated that CIDEA could regulate the expression of FASN and ACACA in the liver and adipose tissue (Zhou et al, 2012;Zhang et al, 2015). In the present study, overexpression of CIDEA increased the abundance of FASN and ACACA and increased TAG content in bovine mammary epithelial cells, indicating some control over the expression of FASN and ACACA.…”

Section: Discussionsupporting

confidence: 62%

High expression of cell death-inducing DFFA-like effector a (CIDEA) promotes milk fat content in dairy cows with clinical ketosis

Sun

Wang

Loor

et al. 2019

Journal of Dairy Science

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High blood concentrations of nonesterified fatty acids (NEFA) during ketosis represent a source of fatty acids for milk fat synthesis and explain the increase in milk fat content in ketotic cows. Cell death-inducing DFFA-like effector a (CIDEA) is a lipid droplet coat protein with important roles in the regulation of milk fat synthesis and secretion in mice. Whether ketosis alters the expression of CIDEA in mammary gland tissue and the extent to which it may contribute to regulation of milk fat synthesis and secretion are unknown. Mammary gland tissue and blood samples were collected from healthy (n = 15) and clinically ketotic (n = 15) cows. Mammary epithelial cells isolated from cows were infected with CIDEA overexpression adenovirus for 48 h, treated with 0, 0.3, 0.6, or 1.2 mM NEFA for 24 h, or infected with CIDEA-silencing adenovirus for 48 h and treated with 1.2 mM NEFA for 24 h. Serum concentrations of NEFA and β-hydroxybutyrate were greater in cows with clinical ketosis, and milk production and dry matter intake were lower in cows with clinical ketosis. However, compared with healthy cows, the content of milk fat of cows with clinical ketosis was greater. Compared with healthy cows, abundance of mRNA and protein of CIDEA, fatty acid synthase (FASN), acetyl-coA carboxylase 1 (ACACA), butyrophilin (BTN1A1), and xanthine dehydrogenase (XDH) was greater in mammary tissue of cows with clinical ketosis. Overexpression of CIDEA in cultured mammary epithelial cells increased the abundance of FASN, ACACA, XDH, and BTN1A1, and increased triacylglycerol (TAG) content in mammary epithelial cells. Exogenous NEFA increased the abundance of CIDEA, FASN, ACACA, XDH, and BTN1A1, and increased TAG content in mammary epithelial cells. Importantly, knockdown of CIDEA reversed the upregulation of FASN, ACACA, XDH, and BTN1A1 abundance and TAG content induced by NEFA treatment. Overall, these data suggest that high levels of NEFA stimulate the expression of CIDEA and enhance de novo fatty acid synthesis and milk fat secretion. As such, these mechanisms explain in part the elevation of milk fat content in dairy cows with clinical ketosis.

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Section: Discussionsupporting

confidence: 62%

High expression of cell death-inducing DFFA-like effector a (CIDEA) promotes milk fat content in dairy cows with clinical ketosis

Sun

Wang

Loor

et al. 2019

Journal of Dairy Science

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“…4B ). Treatment of cultured mammary epithelial cells with BOHB activates SREBF1 and increases the secretion of triacylglycerol 28 . These cell culture models might explain at least one mechanism by which NEB increase the fat content of cows’ milk.…”

Section: Resultsmentioning

confidence: 99%

“…In dairy cows, elevated levels of circulating ketone bodies are associated with an elevated percentage of fat in the milk 28 . In ruminants, BOHB is the main precursor of milk fat synthesis 29 .…”

Section: Resultsmentioning

confidence: 99%

Metabolic gene expression and epigenetic effects of the ketone body β-hydroxybutyrate on H3K9ac in bovine cells, oocytes and embryos

Sangalli

Sampaio

Collado

et al. 2018

Sci Rep

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The rapid decline in fertility that has been occurring to high-producing dairy cows in the past 50 years seems to be associated with metabolic disturbances such as ketosis, supporting the need for research to improve our understanding of the relations among the diet, metabolism and embryonic development. Recently, the ketone body β-hydroxybutyrate (BOHB) was demonstrated to be a potent inhibitor of histone deacetylases (HDACs). Herein, we performed a series of experiments aiming to investigate the epigenetic effects of BOHB on histone acetylation in somatic cells, cumulus-oocyte complexes (COCs) and somatic cell nuclear transfer (SCNT) embryos. Treatment with BOHB does not increase histone acetylation in cells but stimulates genes associated with ketolysis and master regulators of metabolism. We further demonstrated that maturing COCs with high levels of BOHB does not affect their maturation rate or histone acetylation but increases the expression of PPARA in cumulus cells. Treatment of somatic cell nuclear transfer zygotes with BOHB causes hyperacetylation, which is maintained until the blastocyst stage, causing enhanced FOXO3A expression and blastocyst production. Our data shed light on the epigenetic mechanisms caused by BOHB in bovine cells and embryos and provide a better understanding of the connection between nutrition and reproduction.

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“…The RNA was reverse-transcribed to cDNA with the reverse transcription kit (TaKaRa Biotechnology Co., Ltd., Tokyo, Japan) according to the supplier's protocol. The relative expression of the target genes was determined by the 2 -ΔΔCT method [22]. β-actin mRNA was used as an internal control.…”

Section: Rna Extraction and Real-time Quantitative Pcr (Qrt-pcr)mentioning

confidence: 99%

Histamine Induces Bovine Rumen Epithelial Cell Inflammatory Response via NF-κB Pathway

Sun

Xue

Chen

et al. 2017

Cell Physiol Biochem

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103

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Background/Aims: Subacute ruminal acidosis (SARA) is a common disease in highproducing lactating cows. Rumenitis is the initial insult of SARA and is associated with the high concentrations of histamine produced in the rumen of dairy cows during SARA. However, the exact mechanism remains unclear. The objective of the current study is to investigate whether histamine induces inflammation of rumen epithelial cells and the underlying mechanism of this process. Methods: Bovine rumen epithelial cells were cultured and treated with different concentrations of histamine and pyrrolidine dithiocarbamate (PDTC, an NF-κB inhibitor) cultured in different pH medium (pH 7.2 or 5.5). qRT-PCR, Western-blotting, ELISA and immunocytofluorescence were used to evaluate whether histamine activated the NF-κB pathway and inflammatory cytokines. Results: The results showed that histamine significantly increased the activity of IKK β and the phosphorylation levels of IκB α, as well as upregulated the mRNA and protein expression levels of NF-κB p65 in the rumen epithelial cells cultured in neutral (pH=7.2) and acidic (pH=5.5) medium. Furthermore, histamine treatment also significantly increased the transcriptional activity of NF-κB p65. High expression and transcriptional activity of NF-κB p65 significantly increased the mRNA expressions and concentrations of inflammatory cytokines, tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6) and interleukin 1 beta (IL-1β), thereby inducing the inflammatory response in bovine rumen epithelial cells. However, inhibition of NF-κB p65 by PDTC significantly decreased the expressions and concentrations of the inflammatory cytokines induced by histamine in the rumen epithelial cells cultured in the neutral and acidic medium. Conclusion: The present data indicate that histamine induces the inflammatory response of bovine rumen epithelial cells through the NF-κB pathway.X. Sun and X Yuan contributed equally to this study.

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β-Hydroxybutyrate Facilitates Fatty Acids Synthesis Mediated by Sterol Regulatory Element-Binding Protein1 in Bovine Mammary Epithelial Cells

Cited by 32 publications

References 30 publications

High expression of cell death-inducing DFFA-like effector a (CIDEA) promotes milk fat content in dairy cows with clinical ketosis

High expression of cell death-inducing DFFA-like effector a (CIDEA) promotes milk fat content in dairy cows with clinical ketosis

Metabolic gene expression and epigenetic effects of the ketone body β-hydroxybutyrate on H3K9ac in bovine cells, oocytes and embryos

Histamine Induces Bovine Rumen Epithelial Cell Inflammatory Response via NF-κB Pathway

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