# Expression of free fatty acid receptors in the liver of periparturient dairy cows supplemented with essential fatty acids and conjugated linoleic acid

## TL;DR

This study examines how free fatty acid receptors in the liver of dairy cows change around calving and whether adding essential fatty acids or conjugated linoleic acid affects these changes.

## Contribution

The study provides new insights into the expression patterns of hepatic free fatty acid receptors in dairy cows during the periparturient period and their correlation with metabolic parameters.

## Key findings

- FFAR1, FFAR2, and GPR84 expression decreased from pre- to postpartum.
- Supplementation with EFA and CLA had no significant effect on FFAR expression.
- FFAR levels were strongly correlated with each other but weakly linked to other metabolic parameters.

## Abstract

Summary: We studied the expression patterns of hepatic free fatty acid receptors (FFAR) in dairy cows around parturition and early lactation, and the effects of supplementation with essential fatty acids (EFA) and conjugated linoleic acid (CLA) on their expression. Additionally, we investigated the association between hepatic FFAR and other metabolic parameters measured during the transition period. All targeted FFAR were expressed in the liver, except for FFAR4. We found no effects of EFACLA or interactions with time for the expressed FFAR. Expression of FFAR1, FFAR2, and GPR84 decreased from -3 to 9 weeks relative to parturition. FFAR3 levels remained constant from -3 to 4 weeks, then decreased at 9 weeks postpartum. We found strong correlations between FFAR and moderate correlations between FFAR and PPARD. We observed weak links between liver FFAR and other metabolic parameters. Free fatty acid receptor downregulation from pre- to postpartum may prevent receptor hyperactivation during periods of high free fatty acid concentrations. cDNA = complementary deoxyribonucleic acid; RT-qPCR = real-time quantitative polymerase chain reaction. Figure created in BioRender.com.

Summary: We studied the expression patterns of hepatic free fatty acid receptors (FFAR) in dairy cows around parturition and early lactation, and the effects of supplementation with essential fatty acids (EFA) and conjugated linoleic acid (CLA) on their expression. Additionally, we investigated the association between hepatic FFAR and other metabolic parameters measured during the transition period. All targeted FFAR were expressed in the liver, except for FFAR4. We found no effects of EFACLA or interactions with time for the expressed FFAR. Expression of FFAR1, FFAR2, and GPR84 decreased from -3 to 9 weeks relative to parturition. FFAR3 levels remained constant from -3 to 4 weeks, then decreased at 9 weeks postpartum. We found strong correlations between FFAR and moderate correlations between FFAR and PPARD. We observed weak links between liver FFAR and other metabolic parameters. Free fatty acid receptor downregulation from pre- to postpartum may prevent receptor hyperactivation during periods of high free fatty acid concentrations. cDNA = complementary deoxyribonucleic acid; RT-qPCR = real-time quantitative polymerase chain reaction. Figure created in BioRender.com.

•Liver FFAR1, FFAR2, and FFAR3, and GPR84 were downregulated from pre- to postpartum.•Supplementation with EFA and CLA did not affect FFAR.•Expression of liver FFAR were strongly correlated.•PPARD expression peaked at calving and was moderately correlated with FFAR.

Liver FFAR1, FFAR2, and FFAR3, and GPR84 were downregulated from pre- to postpartum.

Supplementation with EFA and CLA did not affect FFAR.

Expression of liver FFAR were strongly correlated.

PPARD expression peaked at calving and was moderately correlated with FFAR.

Free fatty acid receptors (FFAR) are molecular sensors involved in the regulation of energy metabolism. Free fatty acid receptors are expressed in the bovine liver, although their biological functions are not fully understood. Our objectives were to study the expression of hepatic FFAR in periparturient dairy cows supplemented or not with a mixture of essential fatty acids (EFA) and CLA, and to investigate potential associations between FFAR and metabolic adaptation during the transition period. Multiparous Holstein cows received abomasal infusions of either coconut oil (control; n = 8) or a mixture of EFA and CLA (EFACLA; n = 8) from −9 to 9 wk relative to parturition. Liver samples were collected at −3, 0, 4, and 9 wk relative to parturition. We quantified the liver expression of FFAR (FFAR1–4 and GPR84) and peroxisome proliferator-activated receptor delta (PPARD) by real-time quantitative PCR. Repeated-measurement correlations and multilevel multiple factor analysis (MFA) were used to investigate the links between FFAR and other metabolic parameters (i.e., energy balance, blood metabolic indicators, liver proteomics, and liver gene expression). All targeted FFAR were expressed in the liver, except for FFAR4. We found no effects of EFACLA or interactions with time for the expressed FFAR. FFAR1, FFAR2, and GPR84 expression decreased from −3 to 9 wk relative to parturition, whereas FFAR3 remained constant from −3 to 4 wk, then decreased at 9 wk postpartum. We observed strong correlations between FFAR, and moderate correlations between FFAR and PPARD. Multivariate (MFA) and univariate (correlation) analyses revealed weak links between FFAR liver expression and other metabolic parameters (e.g., IGFBP3 liver expression and plasma IGFBP-2). Downregulation of FFAR in the liver from pre- to postpartum may prevent receptors hyperactivation during periods of high free fatty acid concentrations. Physiological relevance and individual contributions of FFAR to the hepatic metabolism require further investigation.