Abstract

Endocannabinoids, particularly anandamide (AEA) and 2-arachidonoylglycerol (2-AG), are instrumental in regulating energy homeostasis and stress response. However, little is known about the endocannabinoid system (ECS) in ruminants, although EC could improve dairy health and productivity, at least by increasing feed intake. In this study, we report if intraperitoneal (i.p.) AEA and 2-AG administration affects feed intake, whole-body macronutrient metabolism, isolation and restraint stress, and whether diet composition modulates circulating endocannabinoid concentrations in cows. Twenty Simmental cows in late lactation were fed a grass silage and a corn silage based diet. On each diet, cows received daily i.p. injections with either AEA (5 µg/kg; n = 7), 2-AG (2.5 µg/kg; n = 6) or saline (n = 7) for 8 days. Endocannabinoid administration for 5 days under free-ranging (non-stressed) conditions had no effect on feed intake or energy balance, but attenuated the stress-induced suppression of feed intake when housing changed to individual tie-stalls without social or tactile interaction. Endocannabinoids increased whole-body carbohydrate oxidation, reduced fat oxidation, and affected plasma non-esterified fatty acid concentrations and fatty acid contents of total lipids. There was no effect of endocannabinoids on plasma triglyceride concentrations or hepatic lipogenesis. Plasma AEA concentrations were not affected by diet, however, plasma 2-AG concentrations tended to be lower on the corn silage based diet. In conclusion, endocannabinoids attenuate stress-induced hypophagia, increase short-term feed intake and whole-body carbohydrate oxidation and decrease whole-body fat oxidation in cows.

Highlights

  • Endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), are instrumental in regulating energy homeostasis and stress response

  • The aim of the present study was to evaluate the effect of i.p. administered AEA and 2-AG administration on isolation and restraint stress, feed intake, milk yield, whole-body macronutrient and hepatic fat metabolism in dairy cows, and to investigate if these effects are influenced by feeding a grass silage (GS) compared to a corn silage (CS) based diet

  • Dry matter intake (DMI) normalized to mBW, Energy balance (EB) and energy corrected milk yield (ECM) did not differ between groups pre-treatment (PB) (Supplementary Fig. S2A) and were higher on the CS than GS diet (P < 0.05)

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Summary

Introduction

Endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), are instrumental in regulating energy homeostasis and stress response. We report if intraperitoneal (i.p.) AEA and 2-AG administration affects feed intake, whole-body macronutrient metabolism, isolation and restraint stress, and whether diet composition modulates circulating endocannabinoid concentrations in cows. Endocannabinoids attenuate stress-induced hypophagia, increase short-term feed intake and whole-body carbohydrate oxidation and decrease whole-body fat oxidation in cows. The best studied endocannabinoids (EC) N-arachidonylethanolamide (anandamide; AEA) and 2-arachidonoylglyerol (2-AG) are synthesized from membrane phospholipids, with fat depots providing an important source for plasma ­EC1 Due to their amphiphilic character, EC can modulate the activity of many membrane proteins and activate the G protein-coupled cannabinoid receptors 1 and 2 (­ CB1 and C­ B2) or the G protein-coupled receptor 55 (GPR55), all of them expressed at the cell ­surface[2,3]. Knowledge about the involvement of the ECS in whole-body energy metabolism is mainly obtained from studies using ­CB1 antagonists (e.g. rimonabant, which is known to exert unwanted side effects) or C­ B1 KO m­ ice[29,30], but there is scarcity of studies using the natural endogenous receptor agonists

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