Review: Pro-inflammatory cytokines and hypothalamic inflammation: implications for insufficient feed intake of transition dairy cows.

Improvements in feed intake of dairy cows entering the early lactation period potentially decrease the risk of metabolic disorders, but before developing approaches targeting the intake level, mechanisms controlling and dysregulating energy balance and feed intake need to be understood. This review focuses on different inflammatory pathways interfering with the neuroendocrine system regulating feed intake of periparturient dairy cows. Subacute inflammation in various peripheral organs often occurs shortly before or after calving and is associated with increased pro-inflammatory cytokine levels. These cytokines are released into the circulation and sensed by neurons located in the hypothalamus, the key brain region regulating energy balance, to signal reduction in feed intake. Besides these peripheral humoral signals, glia cells in the brain may produce pro-inflammatory cytokines independent of peripheral inflammation. Preliminary results show intensive microglia activation in early lactation, suggesting their involvement in hypothalamic inflammation and the control of feed intake of dairy cows. On the other hand, pro-inflammatory cytokine-induced activation of the vagus nerve transmits signalling to the brain, but this pathway seems not exclusively necessary to signal feed intake reduction. Yet, less studied in dairy cows so far, the endocannabinoid system links inflammation and the hypothalamic control of feed intake. Distinct endocannabinoids exert anti-inflammatory action but also stimulate the posttranslational cleavage of neuronal proopiomelanocortin towards β-endorphin, an orexigen promoting feed intake. Plasma endocannabinoid concentrations and hypothalamic β-endorphin levels increase from late pregnancy to early lactation, but less is known about the regulation of the hypothalamic endocannabinoid system during the periparturient period of dairy cows. Dietary fatty acids may modulate the formation of endocannabinoids, which opens new avenues to improve metabolic health and immune status of dairy cows.