International Symposium on Ruminant Physiology: The involvement of the endocannabinoid system in metabolic and inflammatory responses in dairy cows during negative energy balance

The endocannabinoid system (ECS) is involved in the regulation of energy metabolism, immune function and reproduction in mammals. The ECS consists of the endocannabinoid (eCB) ligands, enzymes, and cannabinoid receptors. In mammals, the cannabinoid-1 receptor (CB1/CNR1) is expressed in the central nervous system and in peripheral tissues; and its activation increases anabolic processes. The cannabinoid-2 receptor (CB2/CNR2) is most highly expressed in immune cells, and its activation exerts mainly anti-inflammatory effects. Until recently, little was known about the involvement of the ECS in physiological responses in dairy cows. Because peripartum dairy cows undergo vast changes in energy metabolism and immune function, processes that are regulated by the ECS, several studies have characterized ECS components in transition cows. Concentrations of eCB in the adipose tissue were higher postpartum (PP), and levels of the eCB N-arachidonoylethanolamide (AEA) were increased PP compared with prepartum. Exogenous injections of AEA to transition cows may increase adipose deposition, but did not affect feed intake. In vitro models showed that bovine adipocyte metabolism was differentially affected by CB1 agonists and antagonists in nonlactating nongestating cows compared with PP cows. Thus, the responses of the PP dairy cows to ECS modulations may be related to the physiological and reproductive stage of the cow. Currently, whole-body ECS activation via agonists is mostly not feasible in vivo in livestock. Alternatively, downregulation of ECS activation can be achieved by supplementation of n-3 fatty acids. Indeed, in vivo studies with transition cows supplemented with n-3 showed a moderate downregulation of ECS components in the blood, adipose tissue, and liver, improved systemic insulin sensitivity, but evidently reduced insulin sensitivity in the adipose tissue PP. The abundance of CB1 was lower in immune cells, and anti-inflammatory effects were found in PP cows supplemented with n-3; possibly associating ECS downregulation with immune function. The physiological effect of ECS activation is an exciting and complex area of research that could influence the physiology of dairy cows during metabolic and inflammatory challenges. Dairy cows may be an experimental model for ECS modulations, with broader relevance to female mammals. More research is required on how selective ECS activation and downregulation in tissues could affect immune-metabolic function in dairy cows.