Ketosis is an important
metabolic disease that can negatively affect the production efficiency of dairy cows. Earlier studies have revealed metabolic and inflammatory alterations in the blood associated with
ketosis; however, a link between
ketosis and hepatic
inflammation has not been well documented. The objective of this study was to investigate whether the
nuclear factor kappa B (NF-κB) signaling pathway and NLR family pyrin domain containing 3 (NLRP3)
inflammasome were activated in the liver of ketotic cows. Liver and blood samples were collected from healthy (n = 15, control group) and ketotic (n = 15,
ketosis group) cows that had a similar number of lactations (median = 3, range = 2 to 4) and days in milk (median = 6 d, range = 3 to 9 d). Results showed that serum levels of
fatty acids, β-hydroxybutyrate (BHB),
aspartate aminotransferase (AST), and
alanine aminotransferase (ALT) were higher and
glucose was lower in ketotic cows. Concentrations of serum proinflammatory
cytokines IL18,
tumor necrosis factor (TNF)-α, and IL1B were greater and the anti-inflammatory
cytokine IL10 was lower in the
ketosis group. Cows with
ketosis had
triacylglycerol accumulation in the liver. Upregulation of phosphorylated (p)-NF-κB and p-inhibitor of κB (IκB)α
protein abundance in cows with
ketosis indicated that the hepatic NF-κB signaling pathway was overactivated. The
mRNA abundance of TNFA,
inducible nitric oxide synthase (NOS2),
IL18, and IL1B were greater and
IL10 was lower in ketotic cows. More importantly, the
mRNA and
protein abundance of NLRP3 and caspase-1 (CASP1) along with CASP1 activity were greater in the liver of cows with
ketosis. Overall, the data indicate that the onset of
ketosis is accompanied by activation of the NF-κB signaling pathway and NLRP3
inflammasome, resulting in a state of
inflammation.