Fatty and hydroxycarboxylic acid receptors: The missing link of immune response and metabolism in cattle

Alarcón, Pablo; Manosalva, Carolina; Carretta, María Daniella; Hidalgo, Alejandra I.; Figueroa, Carlos D.; Taubert, Anja; Hermosilla, Carlos; Hidalgo, María A.; Burgos, Rafael A.

doi:10.1016/j.vetimm.2018.05.009

Cited by 17 publications

(13 citation statements)

References 135 publications

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“…In bovines, the high metabolic demands caused by the use of intensive production systems lead to dramatic changes in the levels of BHB. For this, expression of the HCA2 receptor in the immune system and tissues involved in metabolic homeostasis in cattle supports a critical role of this receptor in the innate immune response in these animals 48 . Our results indicated that the expression level of HCA2 mRNA was higher in bovine neutrophils than in kidney adipose tissue.…”

Section: Discussionmentioning

confidence: 61%

β-hydroxybutyrate and hydroxycarboxylic acid receptor 2 agonists activate the AKT, ERK and AMPK pathways, which are involved in bovine neutrophil chemotaxis

Carretta

Barría

Borquez

et al. 2020

Sci Rep

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Elevated plasma concentrations of the ketone body β-hydroxybutyrate (BHB), an endogenous agonist of the hydroxycarboxylic acid receptor 2 (HCA2), is associated with an increased incidence of inflammatory diseases during lactation in dairy cows. In the early stages of this pathology, an increase in neutrophil recruitment is observed; however, the role of BHB remains elusive. This study characterized the effect of BHB and synthetic agonists of the HCA2 receptor on bovine neutrophil chemotaxis and the signaling pathways involved in this process. We demonstrated that treatment with BHB concentrations between 1.2 and 10 mM and two full selective agonists of the HCA2 receptor, MK-1903 and nicotinic acid, increased bovine neutrophil chemotaxis. We also observed that BHB and HCA2 agonists induced calcium release and phosphorylation of AKT, ERK 1/2 and AMPKα. To evaluate the role of these pathways in bovine neutrophil chemotaxis, we used the pharmacological inhibitors BAPTA-AM, pertussis toxin, U73122, LY294002, U0126 and compound C. Our results suggest that these pathways are required for HCA2 agonist-induced bovine neutrophil chemotaxis in non-physiological condition. Concentrations around 1.4 mM of BHB after calving may exert a chemoattractant effect that is key during the onset of the inflammatory process associated with metabolic disorders in dairy cows.

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Section: Discussionmentioning

confidence: 61%

β-hydroxybutyrate and hydroxycarboxylic acid receptor 2 agonists activate the AKT, ERK and AMPK pathways, which are involved in bovine neutrophil chemotaxis

Carretta

Barría

Borquez

et al. 2020

Sci Rep

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“…An excellent review on functions and activation by FA of FFAR in dairy cows was recently published [307]. According to that review, FFAR1 and FFAR4 are activated by LCFA, especially UFA, and FFAR2 and FFAR3 are activated by SCFA.…”

Section: Free Fatty Acid Receptorsmentioning

confidence: 99%

Advances in fatty acids nutrition in dairy cows: from gut to cells and effects on performance

Bionaz

Vargas‐Bello‐Pérez

Busato

2020

J Animal Sci Biotechnol

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High producing dairy cows generally receive in the diet up to 5–6% of fat. This is a relatively low amount of fat in the diet compared to diets in monogastrics; however, dietary fat is important for dairy cows as demonstrated by the benefits of supplementing cows with various fatty acids (FA). Several FA are highly bioactive, especially by affecting the transcriptome; thus, they have nutrigenomic effects. In the present review, we provide an up-to-date understanding of the utilization of FA by dairy cows including the main processes affecting FA in the rumen, molecular aspects of the absorption of FA by the gut, synthesis, secretion, and utilization of chylomicrons; uptake and metabolism of FA by peripheral tissues, with a main emphasis on the liver, and main transcription factors regulated by FA. Most of the advances in FA utilization by rumen microorganisms and intestinal absorption of FA in dairy cows were made before the end of the last century with little information generated afterwards. However, large advances on the molecular aspects of intestinal absorption and cellular uptake of FA were made on monogastric species in the last 20 years. We provide a model of FA utilization in dairy cows by using information generated in monogastrics and enriching it with data produced in dairy cows. We also reviewed the latest studies on the effects of dietary FA on milk yield, milk fatty acid composition, reproduction, and health in dairy cows. The reviewed data revealed a complex picture with the FA being active in each step of the way, starting from influencing rumen microbiota, regulating intestinal absorption, and affecting cellular uptake and utilization by peripheral tissues, making prediction on in vivo nutrigenomic effects of FA challenging.

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“…Herein, we confirmed that TAK-875 induces lipotoxicityinduced β-cell apoptosis by inhibiting the TLR4-NF-κB activation. Accumulating evidence confirmed that GPR40 is associated with immune inflammation [35]. For example, mice lacking GPR40 induced inflammation and insulin resistance in the brain [36].…”

Section: Discussionmentioning

confidence: 97%

TAK-875 Mitigates β-Cell Lipotoxicity-Induced Metaflammation Damage through Inhibiting the TLR4-NF-κB Pathway

Xide

Yan

Weng

et al. 2019

Journal of Diabetes Research

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Metabolic inflammatory damage, characterized by Toll-like receptor 4 (TLR4) signaling activation, is a major mechanism underlying lipotoxicity-induced β-cell damage. The present study is aimed at determining whether G protein-coupled receptor 4 (GPR40) agonist can improve β-cell lipotoxicity-induced damage by inhibiting the TLR4-NF-κB pathway. Lipotoxicity, inflammation-damaged β-cells, obese SD, and TLR4KO rat models were used in the study. In vitro, TAK-875 inhibited the lipotoxicity- and LPS-induced β-cell apoptosis in a concentration-dependent manner, improved the insulin secretion, and inhibited the expression of TLR4 and NF-κB subunit P65. Besides, silencing of TLR4 expression enhanced the protective effects of TAK-875, while TLR4 overexpression attenuated this protective effect. Activation of TLR4 or NF-κB attenuated the antagonism of TAK-875 on PA-induced damage. Moreover, the above process of TAK-875 was partially independent of GPR40 expression. TAK-875 reduced the body weight and inflammatory factors, rebalanced the number and distribution of α or β-cells, inhibited the apoptosis of islet cells, and inhibited the expression of TLR4 and NF-κB subunit P65 in obese rats. Further knockout of the rat TLR4 gene delayed the damage induced by the high-fat diet and synergy with the action of TAK-875. These data suggest that GPR40 agonists antagonized the lipotoxicity β-cell damage by inhibiting the TLR4-NF-κB pathway.

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Fatty and hydroxycarboxylic acid receptors: The missing link of immune response and metabolism in cattle

Cited by 17 publications

References 135 publications

β-hydroxybutyrate and hydroxycarboxylic acid receptor 2 agonists activate the AKT, ERK and AMPK pathways, which are involved in bovine neutrophil chemotaxis

β-hydroxybutyrate and hydroxycarboxylic acid receptor 2 agonists activate the AKT, ERK and AMPK pathways, which are involved in bovine neutrophil chemotaxis

Advances in fatty acids nutrition in dairy cows: from gut to cells and effects on performance

TAK-875 Mitigates β-Cell Lipotoxicity-Induced Metaflammation Damage through Inhibiting the TLR4-NF-κB Pathway

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