Dietary Fish Oil Inhibits Pro-Inflammatory and ER Stress Signalling Pathways in the Liver of Sows during Lactation

Abstract

Lactating sows have been shown to develop typical signs of an inflammatory condition in the liver during the transition from pregnancy to lactation. Hepatic inflammation is considered critical due to the induction of an acute phase response and the activation of stress signaling pathways like the endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR), both of which impair animal´s health and performance. Whether ER stress-induced UPR is also activated in the liver of lactating sows and whether dietary fish oil as a source of anti-inflammatory effects n-3 PUFA is able to attenuate hepatic inflammation and ER stress-induced UPR in the liver of sows is currently unknown. Based on this, two experiments with lactating sows were performed. The first experiment revealed that ER stress-induced UPR occurs also in the liver of sows during lactation. This was evident from the up-regulation of a set of genes regulated by the UPR and numerically increased phosphorylation of the ER stress-transducer PERK and PERK-mediated phosphorylation of eIF2α and IκB. The second experiment showed that fish oil inhibits ER stress-induced UPR in the liver of lactating sows. This was demonstrated by decreased mRNA levels of a number of UPR-regulated genes and reduced phosphorylation of PERK and PERK-mediated phosphorylation of eIF2α and IκB in the liver of the fish oil group. The mRNA levels of various nuclear factor-κB-regulated genes encoding inflammatory mediators and acute phase proteins in the liver of lactating sows were also reduced in the fish oil group. In line with this, the plasma levels of acute phase proteins were reduced in the fish oil group, although differences to the control group were not significant. In conclusion, ER stress-induced UPR is present in the liver of lactating sows and fish oil is able to inhibit inflammatory signaling pathways and ER stress-induced UPR in the liver.

Potential of plant polyphenols to combat oxidative stress and inflammatory processes in farm animals

“…(), 4‐week intraduodenal supplementation of quercetin did not influence mRNA concentrations of various antioxidant enzymes in the liver of dairy cows. In a recent study of our group, supplementation of polyphenol‐rich grape seed and grape marc meal extract at a dietary level of 1% also did not improve the plasma antioxidant status of dairy cows (as assessed by determination of α‐tocopherol, β‐carotene, TBARS and total antioxidative capacity in plasma) (Gessner et al., ). In another study, feeding a polyphenol‐rich plant product consisting of green tea and curcuma extract also did not exert antioxidant effects in dairy cows (Winkler et al., ).…”

“…These results led the authors to suggest that feeding pomegranate extract polyphenols suppresses nutrient digestibility, likely because of the high tannin content, but enhances mitogen-induced cytokine production and response to vaccination, which might be beneficial for immune competence and health of calves. In the study from Gessner et al (2015a), feeding a polyphenol-rich grape seed and grape marc meal extract in dairy cows caused a consistent reduction (25-65%) of the mRNA concentrations of a large set of genes involved in inflammation and ER stress in the liver, even though the effects were not statistically significant. Moreover, feeding grape seed and grape marc meal extract to dairy cows in that study caused a significant downregulation of fibroblast growth factor (FGF)-21, a key marker of ER stress and a surrogate marker of liver fat accumulation.…”

“…In the study from Gessner et al. (), feeding a polyphenol‐rich grape seed and grape marc meal extract in dairy cows caused a consistent reduction (25–65%) of the mRNA concentrations of a large set of genes involved in inflammation and ER stress in the liver, even though the effects were not statistically significant. Moreover, feeding grape seed and grape marc meal extract to dairy cows in that study caused a significant downregulation of fibroblast growth factor (FGF)‐21, a key marker of ER stress and a surrogate marker of liver fat accumulation.…”

“…Recent studies have shown that lactation is another metabolic condition which is associated with the development of inflammation in the liver of pigs (Rosenbaum et al., ,b). It is likely that the induction of inflammation in the liver of lactating sows – which was also associated with the development of stress of the endoplasmic reticulum (ER stress), a condition triggered by inflammation – might be due to oxidative stress caused by the high metabolic activity or the occurrence of infectious diseases such as mastitis or metritis which are commonly observed in sows after parturition (Gessner et al., ,b). Physiological consequences of inflammatory conditions in lactating sows have been less investigated so far.…”

“…Conversely, inhibition of the proinflammatory condition during the peripartal phase in dairy cows by early post‐partum treatment with non‐steroidal anti‐inflammatory drugs led to a significant increase in milk yield over the whole lactation period and caused a reduction in somatic cell count in milk being indicative of an improved udder health (Carpenter et al., ). According to these findings, investigations aiming to prevent the proinflammatory condition during the peripartal phase, either by optimization of feeding regimes pre‐partum (Khan et al., ; Zhou et al., ; Vailati‐Riboni et al., ) or by administration of potential antiinflammatory feed supplements (Gessner et al., ,b; Hashemzadeh‐Cigari et al., ; Winkler et al., ), are of great relevance.…”