Sirtuin 3 inhibits nuclear factor-κB signaling activated by a fatty acid challenge in bovine mammary epithelial cells

Susceptibility to mastitis is highest during the peripartal (transition) period and often concomitant with other comorbidities such as ketosis. Although infection pathogenic microorganisms immune-dysfunction around calving clearly play key roles in development, metabolic factors also contribute. Sirtuin 3 (SIRT3), a mitochondrial deacetylase regulating energy redox homeostasis, antagonizes lipotoxic effects of nonesterified fatty acids (NEFA). Thus, we hypothesized that increases circulating NEFA concentrations, observed transition period, provokes inflammatory responses can be reversed via activation SIRT3. Here aimed study (1) proinflammatory NF-κB signaling SIRT3 abundance mammary tissue ketotic cows healthy controls, (2) effect on bovine epithelial cells (BMEC) treated high levels NEFA. The gland biopsy samples were from previous study, which included 15 cows. Primary BMEC isolated Holstein collagenase III digestion. Purified incubated or without overexpression adenovirus for 48 h, then 0, 0.6, 1.2, 2.4 mM 24 h. Mammary was associated lower protein along greater P65 phosphorylation (p-NF-κB P65), p-NF-κB P65:NF-κB ratio, mRNA IL1B IL6. In BMEC, exogenous dose-dependently reduced SIRT3, but increased P65, Compared green fluorescent vector + NEFA, NEFA-treated downregulated Immunofluorescence indicated inhibited nuclear translocation P65. Overall, our data demonstrated ketosis reduction gland. vitro provided evidence concentrations inhibit contributes enhanced including pro-inflammatory response. suggest promising role target helping alleviate localized inflammation resulting exposure