Effects of increasing acetate, butyrate, and β-hydroxybutyrate on expression of lipogenic genes in bovine mammary epithelial cell culture
- 1Department of Animal Science, Penn State University, University Park, PA 16802
Abstract
Acetate and butyrate are the main lipogenic short-chain fatty acids (SCFA). β-Hydroxybutyrate is synthesized primarily from butyrate and can also serve as a substrate for mammary de novo fatty acid synthesis. Acetate supplementation in vivo increases milk fat yield, but the direct effects of SCFA and BHB on transcriptional regulation of lipid synthesis in mammary epithelial cells remain unclear. This study was designed to specifically evaluate the direct effects of increasing sodium butyrate, sodium acetate, and BHB on lipogenic gene expression in mammary epithelial cells (MAC-T). Cells were treated for 24 h with 0, 4, 8, or 12 mM of each, and expression of the ACSS2, ACACA, FASN, SCD1, INSIG1, and SREBF1C genes were analyzed. Butyrate increased lipogenic genes to the greatest extent, with a dramatic increase in SREBF1c (>14-fold at 12 mM), FASN, ACACA, and SCD1. Sodium acetate had modest effects, increasing ACSS2 and SCD1 expression without broad activation of other lipogenic genes. However, BHB increased FASN (∼16-fold at 8 mM) but had minimal effects on SREBF1c, INSIG1, or SCD1. We found that BHB also increased PPARG and FABP3, which was not observed with acetate or butyrate. In summary, butyrate strongly increased expression of mammary lipogenic genes, consistent with both its role as a preferred primer for fatty acid synthesis and reported HDAC-inhibitory activity. Acetate and BHB exerted more limited, pathway-specific responses, underscoring potentially distinct mechanisms of SCFA-mediated regulation of expression of lipid metabolism enzymes in the mammary gland. Future work will be needed to determine the functional roles on the rate of lipid synthesis.
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BibTeX
@article{haile2026effects,
title = {{Effects of increasing acetate, butyrate, and β-hydroxybutyrate on expression of lipogenic genes in bovine mammary epithelial cell culture}},
author = {Abiel Haile and Kevin J. Harvatine},
journal = {JDS communications},
year = {2026},
month = aug,
doi = {10.3168/jdsc.2026-1091},
url = {https://europepmc.org/article/PMC/PMC13751261},
note = {CC BY},
}
RIS
TY - JOUR
TI - Effects of increasing acetate, butyrate, and β-hydroxybutyrate on expression of lipogenic genes in bovine mammary epithelial cell culture
AU - Abiel Haile
AU - Kevin J. Harvatine
PY - 2026
DA - 2026/08/03
JO - JDS communications
DO - 10.3168/jdsc.2026-1091
UR - https://europepmc.org/article/PMC/PMC13751261
AB - Acetate and butyrate are the main lipogenic short-chain fatty acids (SCFA). β-Hydroxybutyrate is synthesized primarily from butyrate and can also serve as a substrate for mammary de novo fatty acid synthesis. Acetate supplementation in vivo increases milk fat yield, but the direct effects of SCFA and BHB on transcriptional regulation of lipid synthesis in mammary epithelial cells remain unclear. This study was designed to specifically evaluate the direct effects of increasing sodium butyrate, sodium acetate, and BHB on lipogenic gene expression in mammary epithelial cells (MAC-T). Cells were treated for 24 h with 0, 4, 8, or 12 mM of each, and expression of the ACSS2, ACACA, FASN, SCD1, INSIG1, and SREBF1C genes were analyzed. Butyrate increased lipogenic genes to the greatest extent, with a dramatic increase in SREBF1c (>14-fold at 12 mM), FASN, ACACA, and SCD1. Sodium acetate had modest effects, increasing ACSS2 and SCD1 expression without broad activation of other lipogenic genes. However, BHB increased FASN (∼16-fold at 8 mM) but had minimal effects on SREBF1c, INSIG1, or SCD1. We found that BHB also increased PPARG and FABP3, which was not observed with acetate or butyrate. In summary, butyrate strongly increased expression of mammary lipogenic genes, consistent with both its role as a preferred primer for fatty acid synthesis and reported HDAC-inhibitory activity. Acetate and BHB exerted more limited, pathway-specific responses, underscoring potentially distinct mechanisms of SCFA-mediated regulation of expression of lipid metabolism enzymes in the mammary gland. Future work will be needed to determine the functional roles on the rate of lipid synthesis.
SN - 2666-9102
ER -