Possible involvement of the RARRES2/CMKLR1-system in metabolic and reproductive parameters in Holstein dairy cows

Abstract

Background In dairy cows, the energy cost of milk yield results in a negative energy balance (EB) and body fat mobilization that impairs reproductive efficiency. Emerging evidence suggests that the novel adipokines, Retinoic acid receptor responder protein 2 (RARRES2), and its main receptor, Chemokine-like receptor 1 (CMKLR1) are involved in the regulation of metabolic and ovarian functions. So, we investigated in a first experiment the plasma RARRES2, and RARRES2 and CMKLR1 mRNA expression levels in subcutaneous adipose tissue (SAT) and granulosa cells (GC) at different times of body fat mobilization in dairy cows (4, 8, 20 and 44 weeks postpartum, wk. pp. for SAT and 8, 20 and 44 wk. pp. for GC). Then, in a second experiment we examined the effect of high (HE) and low energy (LE) diets on the RARRES2 system and its links with metabolic and reproductive parameters. Methods The first experiment included 9 animals fed with HE diet from 4 to 44 wk. pp. and the second one included animals fed either a HE diet ( n = 8) or a LE diet ( n = 8) from − 4 to 16 wk. peripartum. In both experiments, various metabolic and reproductive parameters were determined and associated with plasma RARRES2 as measured by bovine ELISA. RARRES2 and CMKLR1 mRNA expression levels were analyzed by RT-qPCR in SAT after biopsy and GC after aspiration of follicles. Results Plasma RARRES2 levels were higher at 4 wk. pp. as compared to 20 and 44 wk. pp. and they were positively correlated with body fat mobilization and milk yield. RARRES2 and CMKLR1 mRNA expression levels increased from 4 to 8 wk. pp. (fat mobilization, EB < 0) and remained unchanged at 20 and 44 wk. pp. (fat reconstitution, EB > 0) as compared to 4 wk. pp. in SAT. RARRES2 and CMKLR1 mRNA levels decreased from 8 to 44 wk. pp. in GC from small follicles. In the second experiment, plasma RARRES2 increased from − 4 to 8 wk. peripartum similarly in both LE and HE cows. In addition, the area under of plasma RARRES2 curve was highly negatively associated with the number of small follicles obtained in HE animals during the cycle before the first artificial insemination. In SAT of HE cows, RARRES2 mRNA expression decreased at 1 wk. pp. compared to − 4 and 16 wk. peripartum whereas opposite expression patterns were obtained for CMKLR1. Similar results were observed for CMKLR1 mRNA expression in LE cows while there was no variation in RARRES2 mRNA expression. Moreover, RARRES2 mRNA was higher expressed in LE than in HE cows at 1 wk. pp. Conclusions The lactation-induced fat and energy mobilization influenced plasma RARRES2 profile and mRNA expression pattern of RARRES2 and CMKLR1 similarly in both SAT and GC. In addition, the energy content of the diet did not affect plasma RARRES2 but it altered RARRES2 mRNA expression in SAT and the area under the curve of plasma RARRES2 that was negatively associated to the number of small follicl...

Adipokines as biomarkers of postpartum subclinical endometritis in dairy cows

“…Plasma and uterine fluid total ADIPOQ, RARRES2 and NAMPT concentrations were measured by using ELISA kits (E11A0125 and E11C0104 from BlueGene, Shanghai, China and EK-003-80 from Phoenix France, SAS, Strasbourg, France, respectively), as previously described ( Fadden & Bobe 2016 , Mellouk et al 2017 , 2019 ). The intra-assay coefficients of variation for total ADIPOQ, RARRES2 and NAMPT were 6%, 4.5% and 6.5%, respectively.…”

“…The activation of CMKLR1 by RARRES2 induces the migration of macrophages and dendritic cells in vitro , which supports the proinflammatory role of the RARRES2/CMKLR1 axis ( Yoshimura & Oppenheim 2011 ). In cows, RARRES2 was referred as a mediator, linking metabolism and ovarian function, and plasma concentrations are positively correlated with body fat mobilization and milk yield ( Mellouk et al 2019 ).…”

Symposium review: Adipose tissue endocrinology in the periparturient period of dairy cows

“…Chemerin is involved in the regulation of the immune system, inflammation, angiogenesis, adipogenesis, and glucose metabolism in humans (Helfer and Wu, 2018). In dairy cows, plasma concentrations of chemerin range from 3.6 to 4.8 ng/mL in early lactation and then steadily decrease until wk 20 of lactation (Mellouk et al, 2019). The mRNA abundance of RARRES2 in bovine scAT was related to BCS and yearling weight (Lindholm-Perry et al, 2012), adipocyte differentiation (Song et al, 2010), and body fat mobilization (Elis et al, 2013(Elis et al, , 2016Mellouk et al, 2019).…”

“…In dairy cows, plasma concentrations of chemerin range from 3.6 to 4.8 ng/mL in early lactation and then steadily decrease until wk 20 of lactation (Mellouk et al, 2019). The mRNA abundance of RARRES2 in bovine scAT was related to BCS and yearling weight (Lindholm-Perry et al, 2012), adipocyte differentiation (Song et al, 2010), and body fat mobilization (Elis et al, 2013(Elis et al, , 2016Mellouk et al, 2019). Fu et al (2016) investigated the effects of chemerin treatment on mature adipocytes as well as de-differentiated bovine intramuscular preadipocytes in vitro.…”

Irisin and the fibronectin type III domain-containing family: structure, signaling and role in female reproduction

“…During NEB, the mobilization of fat reserves alters adipokine secretion, for example, plasma adiponectin and leptin concentrations have been observed to decrease at parturition in cattle (Mellouk et al 2017), whereas plasma resistin and chemerin concentrations increase (Reverchon et al 2014b, Mellouk et al 2019. All these adipokines are also able to modulate in vitro ovarian steroidogenesis (Kurowska et al 2021).…”