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Embryonic response to high beta-hydroxybutyrate (BHB) levels in postpartum dairy cows [gene expression]

ABSTRACT: This project is meant to document the effect of the negative energetic balance on the embryo quality and as it happens, to identify ways to improve the fertility of dairy bovines. Measurement of the β-Hydroxybutyric acid (BHB) has been taken between 45 and 60 days post-partum on twelve Holstein cows. Cows have been ranked according to the sanguine measurement as high or low in BHB in order to get 6 cows per group. After having synchronized the heat with hormones and an ovarian stimulation, cows have been inseminated and the embryos were selected as so to be transferred in at least two heifers. This project aim at isolating the differences created on the transcriptomic expression in morulas and blastocysts grown in cows with an energetic inbalance.

ORGANISM(S): Bos taurus

PROVIDER: GSE122601 | GEO | 2019/11/14

REPOSITORIES: GEO

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Project description:Beta-hydroxybutyrate (BHB) is a ketone body synthesized during fasting or strenuous exercise. Our previous study demonstrated that a cyclic ketogenic diet (KD), which induces BHB levels similar to fasting every other week, reduces midlife mortality and improves memory in aging mice. BHB actively regulates gene expression and inflammatory activation through non-energetic signaling pathways. Neither of these activities has been well-characterized in the brain and they may represent mechanisms by which BHB affects brain function during aging. First, we analyzed hepatic gene expression in an aging KD-treated mouse cohort using bulk RNA-seq. In addition to the downregulation of TOR pathway activity, cyclic KD reduces inflammatory gene expression in the liver. We observed via flow cytometry that KD also modulates age-related systemic T cell functions. Next, we investigated whether BHB affects brain cells transcriptionallyin vitro. Gene expression analysis in primary human brain cells (microglia, astrocytes, neurons) using RNA-seq shows that BHB causes a mild level of inflammation in all three cell types. However, BHB inhibits the more pronounced LPS-induced inflammatory gene activation in microglia. Furthermore, we confirmed that BHB similarly reduces LPS-induced inflammation in primary mouse microglia and bone marrow-derived macrophages (BMDMs). BHB is recognized as an inhibitor of histone deacetylase (HDAC), an inhibitor of NLRP3 inflammasome, and an agonist of the GPCR Hcar2. Nevertheless, in microglia, BHB's anti-inflammatory effects are independent of these known mechanisms. Finally, we examined the brain gene expression of 12-month-old male mice fed with one-week and one-year cyclic KD. While a one-week KD increases inflammatory signaling, a one-year cyclic KD reduces neuroinflammation induced by aging. In summary, our findings demonstrate that BHB mitigates the microglial response to inflammatory stimuli, like LPS, possibly leading to decreased chronic inflammation in the brain after long-term KD treatment in aging mice.

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Embryonic response to high beta-hydroxybutyrate (BHB) levels in postpartum dairy cows [gene expression]

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