Cell death-inducing DNA fragmentation factor-α-like effector C (CIDEC) regulates acetate- and β-hydroxybutyrate-induced milk fat synthesis by increasing FASN expression in mammary epithelial cells of dairy cows

Abstract

Increasing acetate and β-hydroxybutyrate (BHB) supply to lactating cows will increase milk fat synthesis. However, the underlying molecular mechanism remains largely unknown. Cell death-inducing DNA fragmentation factor-α-like effector C (CIDEC) is a lipid dropletassociated protein that promotes intracellular triacylglycerol accumulation. In the present study, using gene overexpression and knockdown, we detected the contributions of CIDEC on milk fat synthesis in mammary epithelial cells of dairy cows in the presence of acetate and BHB. The results showed that knockdown of CIDEC decreased fatty acid synthase (FASN) expression and intracellular triacylglycerol content, whereas overexpression of CIDEC had the opposite effect. The transcription factor CCAAT/enhancer-binding protein β (C/EBPβ) regulates cell growth and differentiation in the mammary gland. We demonstrated that the FASN promoter had a canonical C/EBPβ binding sequence. CEBPB overexpression upregulated FASN expression and milk fat synthesis, whereas CEBPB knockdown had the opposite effect. Moreover, knockdown of CEBPB attenuated the promoting effects of CIDEC on acetateand BHB-induced FASN transcription. Taken together, our data showed that acetate and BHB induced FASN expression in mammary epithelial cells of dairy cows in a CIDEC-C/EBPβ-dependent manner, which provides new insights into the understanding of the molecular events involved in milk fat synthesis.

Acetate Upregulates GPR43 Expression and Function via PI3K-AKT-SP1 Signaling in Mammary Epithelial Cells during Milk Fat Synthesis

“…Acetate is the main lipogenic substrate in the process of de novo FA production within mammary tissues of dairy cows. 2 As a Gprotein-coupled receptor, GPR43 is related to adipocyte differentiation. 24 Our study demonstrated that GPR43 was highly expressed within mammary tissues in lactating cows and functioned in milk fat production.…”

“…Acetate is the main lipogenic substrate in the process of de novo FA production within mammary tissues of dairy cows . As a G-protein-coupled receptor, GPR43 is related to adipocyte differentiation .…”

“…Milk fat is a valuable component of milk, which provides nutrients and energy to humans. , Acetate accounts for a main rumen fermentation product in cows, which can promote the synthesis of milk fat in lactating dairy cows in a dose-dependent manner by increasing de novo fatty acid (FA) biosynthesis. − Consequently, the acetate supply has a certain effect on milk fat production within lactating cows.…”

MSI2 Modulates Unsaturated Fatty Acid Metabolism by Binding FASN in Bovine Mammary Epithelial Cells

“…FASN is a key enzyme in the regulation of the de novo synthesis of milk lipids. In BMECs, cell-death-induced DNA fragmentation factor α-like effector C (CIDEC) regulates acetate-induced milk fat synthesis by increasing FASN expression . In buffalo mammary glands, liver X receptor α (LXRα) promotes milk fat synthesis by regulating FASN expression through direct interactions with the FASN promoter .…”

PPARγ-AGPAT6 signaling mediates acetate-induced mTORC1 activation and milk fat synthesis in mammary epithelial cells of dairy cows

“…Mammary tissue samples from 3 lactating cows at 90 DIM were used for mammary epithelial cell isolation. Cells were cultured in DMEM/F12 supplemented with 10% FBS, penicillin (100U/mL), and streptomycin (100μg/mL) as previously described (Lv et al ., 2021).…”