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Invited review: nutrient-sensing receptors for free fatty acids and hydroxycarboxylic acids in farm animals

  • M. Mielenz (a1)

Data on nutrient sensing by free fatty acid receptors (FFAR1, FFAR2, FFAR3, FFAR4) and hydroxycarboxylic acid receptors (HCAR1, HCAR2) are increasing for human or rodent models. Both receptor families link intestinal fermentation by the microbiota and energy metabolism with cellular responses. Therefore, this finding provides a link that is independent of the only function of the fermentation products as energy substrates. For example, these reactions are associated with insulin secretion, regulation of lipolysis, adipose tissue differentiation and innate immune responses. In farm animals, the available data on both receptor families from the intestine and other tissues increase. However, currently, the data are primarily linked with the distribution of receptor messenger RNAs (mRNAs) and more rarely with proteins. Functional data on the importance of these receptors in farm animal species is not abundant and is often associated with the immune system. In certain farm animal species, the receptors were cloned and ligand binding was characterised. In chicken, only one FFAR2 was recently identified using genome analysis, which is contradictory to a study using an FFAR1 small interfering RNA. The chicken FFAR2 is composed of more than 20 paralogs. No data on HCAR1 or HCAR2 exist in this species. Currently, in pigs, most available data are on the mRNA distribution within intestine. However, no FFAR1 expression has been shown in this organ to date. In addition to FFAR2, an orthologue (FFAR2-like) with the highest abundance in intestine has been reported. The data on HCAR1 and HCAR2 in pigs is scarce. In ruminants, most of the currently available information on receptor distribution is linked to mRNA data and shows the expression, for example, in mammary gland and adipose tissue. However, some protein data on FFAR2 and FFAR1 protein has been reported and functional data availability is slowly increasing. The receptor mRNAs of HCAR1 and HCAR2 are expressed in bovine. The HCAR2 protein has been demonstrated in certain tissues, such as liver and fat. Because of the physiological importance of both receptor families in human life science, more studies that analyse the physiological significance of both receptor families in animal science may be performed within the next several years.

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References dated before 2013 are presented as Supplementary Materials.
Aguinaga Casañas, MA, Schäff, CT, Albrecht, E, Hammon, HM, Kuhla, B, Röntgen, M, Nürnberg, G and Mielenz, M submitted. Free fatty acid receptors FFAR1 and FFAR2 during the peripartal period in liver of dairy cows which were grouped by their plasma beta-hydroxybutyrate concentrations postpartum. Journal of Dairy Science.
Alvarez-Curto, E and Milligan, G 2016. Metabolism meets immunity: the role of free fatty acid receptors in the immune system. Biochememical Pharmacology 114, 313.
Chen, K, Zhou, JD, Zhang, F, Zhang, F, Zhang, RR, Zhan, MS, Tang, XY, Deng, B, Lei, MG and Xiong, YZ 2016. Transcription factor C/EBPbeta promotes the transcription of the porcine GPR120 gene. Journal of Molecular Endocrinology 56, 91100.
Christensen, LW, Kuhre, RE, Janus, C, Svendsen, B and Holst, JJ 2015. Vascular, but not luminal, activation of FFAR1 (GPR40) stimulates GLP-1 secretion from isolated perfused rat small intestine. Physiological Reports 3, e12551.
Efeyan, A, Comb, WC and Sabatini, DM 2015. Nutrient-sensing mechanisms and pathways. Nature 517, 302310.
Engelstoft, MS, Park, WM, Sakata, I, Kristensen, LV, Husted, AS, Osborne-Lawrence, S, Piper, PK, Walker, AK, Pedersen, MH, Nohr, MK, Pan, J, Sinz, CJ, Carrington, PE, Akiyama, TE, Jones, RM, Tang, C, Ahmed, K, Offermanns, S, Egerod, KL, Zigman, JM and Schwartz, TW 2013. Seven transmembrane G protein-coupled receptor repertoire of gastric ghrelin cells. Molecular Metabolism 2, 376392.
Fontanesi, L, Bertolini, F, Scotti, E, Schiavo, G, Colombo, M, Trevisi, P, Ribani, A, Buttazzoni, L, Russo, V and Dall’Olio, S 2015. Next generation semiconductor based-sequencing of a nutrigenetics target gene (GPR120) and association with growth rate in Italian Large White pigs. Animal Biotechnology 26, 9297.
Friedrichs, P, Saremi, B, Winand, S, Rehage, J, Danicke, S, Sauerwein, H and Mielenz, M 2014. Energy and metabolic sensing G protein-coupled receptors during lactation-induced changes in energy balance. Domestic Animal Endocrinology 48, 3341.
Friedrichs, P, Sauerwein, H, Huber, K, Locher, LF, Rehage, J, Meyer, U, Danicke, S, Kuhla, B and Mielenz, M 2016. Expression of metabolic sensing receptors in adipose tissues of periparturient dairy cows with differing extent of negative energy balance. Animal 10, 623632.
Graff, EC, Fang, H, Wanders, D and Judd, RL 2016. Anti-inflammatory effects of the hydroxycarboxylic acid receptor 2. Metabolism 65, 102113.
Haenen, D, Zhang, J, Souza da Silva, C, Bosch, G, van der Meer, IM, van Arkel, J, van den Borne, JJ, Perez Gutierrez, O, Smidt, H, Kemp, B, Muller, M and Hooiveld, GJ 2013. A diet high in resistant starch modulates microbiota composition, SCFA concentrations, and gene expression in pig intestine. Journal of Nutrition 143, 274283.
Hamilton Weatherburn, D 2015. Role of short chain fatty acid receptors in the gastrointestinal tract and their potential involvement in appetite control. PhD thesis, University of Liverpool, Liverpool, Great Britain. Retrieved on 19 February 2016 from
Hara, T, Ichimura, A and Hirasawa, A 2014. Therapeutic role and ligands of medium- to long-chain fatty acid receptors. Frontiers in Endocrinology (Lausanne) 5, 83.
Harrison, OJ, Srinivasan, N, Pott, J, Schiering, C, Krausgruber, T, Ilott, NE and Maloy, KJ 2015. Epithelial-derived IL-18 regulates Th17 cell differentiation and Foxp3(+) Treg cell function in the intestine. Mucosal Immunology 8, 12261236.
Hoque, R, Farooq, A, Ghani, A, Gorelick, F and Mehal, WZ 2014. Lactate reduces liver and pancreatic injury in Toll-like receptor- and inflammasome-mediated inflammation via GPR81-mediated suppression of innate immunity. Gastroenterology 146, 17631774.
Janssen, S and Depoortere, I 2013. Nutrient sensing in the gut: new roads to therapeutics? Trends in Endocrinology & Metabolism 24, 92100.
Ji, P, Drackley, JK, Khan, MJ and Loor, JJ 2014. Overfeeding energy upregulates peroxisome proliferator-activated receptor (PPAR) gamma-controlled adipogenic and lipolytic gene networks but does not affect proinflammatory markers in visceral and subcutaneous adipose depots of Holstein cows. Journal of Dairy Science 97, 34313440.
Jiang, RR, Zhao, GP, Zhao, JP, Chen, JL, Zheng, MQ, Liu, RR and Wen, J 2014. Influence of dietary nicotinic acid supplementation on lipid metabolism and related gene expression in two distinct broiler breeds of female chickens. Journal of Animal Physiology and Animal Nutrition (Berl) 98, 822829.
Jobin, C 2014. GPR109a: the missing link between microbiome and good health? Immunity 40, 810.
Kenez, A, Locher, L, Rehage, J, Danicke, S and Huber, K 2014. Agonists of the G protein-coupled receptor 109A-mediated pathway promote antilipolysis by reducing serine residue 563 phosphorylation of hormone-sensitive lipase in bovine adipose tissue explants. Journal of Dairy Science 97, 36263634.
Khan, M, Couturier, A, Kubens, JF, Most, E, Mooren, FC, Kruger, K, Ringseis, R and Eder, K 2013b. Niacin supplementation induces type II to type I muscle fiber transition in skeletal muscle of sheep. Acta Veterinaria Scandinavica 55, 85.
Khan, M, Ringseis, R, Mooren, FC, Kruger, K, Most, E and Eder, K 2013a. Niacin supplementation increases the number of oxidative type I fibers in skeletal muscle of growing pigs. BMC Veterinary Research 9, 177.
Kimura, I, Ozawa, K, Inoue, D, Imamura, T, Kimura, K, Maeda, T, Terasawa, K, Kashihara, D, Hirano, K, Tani, T, Takahashi, T, Miyauchi, S, Shioi, G, Inoue, H and Tsujimoto, G 2013. The gut microbiota suppresses insulin-mediated fat accumulation via the short-chain fatty acid receptor GPR43. Nature Communications 4, 1829.
Kokrashvili, Z, Yee, KK, Ilegems, E, Iwatsuki, K, Li, Y, Mosinger, B and Margolskee, RF 2014. Endocrine taste cells. British Journal of Nutrition 111 (Suppl 1), S23S29.
Konno, Y, Ueki, S, Takeda, M, Kobayashi, Y, Tamaki, M, Moritoki, Y, Oyamada, H, Itoga, M, Kayaba, H, Omokawa, A and Hirokawa, M 2015. Functional analysis of free fatty acid receptor GPR120 in human eosinophils: implications in metabolic homeostasis. PLoS ONE 10, e0120386.
Kopp, C, Hosseini, A, Singh, SP, Regenhard, P, Khalilvandi-Behroozyar, H, Sauerwein, H and Mielenz, M 2014. Nicotinic acid increases adiponectin secretion from differentiated bovine preadipocytes through G-protein coupled receptor signaling. International Journal of Molecular Sciences 15, 2140121418.
Kristinsson, H, Bergsten, P and Sargsyan, E 2015. Free fatty acid receptor 1 (FFAR1/GPR40) signaling affects insulin secretion by enhancing mitochondrial respiration during palmitate exposure. Biochimica et Biophysica Acta 1853, 32483257.
Li, G, Su, H, Zhou, Z and Yao, W 2014b. Identification of the porcine G protein-coupled receptor 41 and 43 genes and their expression pattern in different tissues and development stages. PLoS ONE 9, e97342.
Li, G, Yao, W and Jiang, H 2014a. Short-chain fatty acids enhance adipocyte differentiation in the stromal vascular fraction of porcine adipose tissue. Journal of Nutrition 144, 18871895.
Loaiza, A, Carretta, MD, Taubert, A, Hermosilla, C, Hidalgo, MA and Burgos, RA. 2016. Differential intracellular calcium influx, nitric oxide production, ICAM-1 and IL8 expression in primary bovine endothelial cells exposed to nonesterified fatty acids. BMC Veterinary Research 12, 38.
Mancini, AD, Bertrand, G, Vivot, K, Carpentier, E, Tremblay, C, Ghislain, J, Bouvier, M and Poitout, V 2015. Beta-Arrestin recruitment and biased agonism at free fatty acid receptor 1. The Journal of Biological Chemistry 290, 2113121140.
Manosalva, C, Mena, J, Velasquez, Z, Colenso, CK, Brauchi, S, Burgos, RA and Hidalgo, MA 2015. Cloning, identification and functional characterization of bovine free fatty acid receptor-1 (FFAR1/GPR40) in neutrophils. PLoS ONE 10, e0119715.
Matis, G, Kulcsar, A, Turowski, V, Febel, H, Neogrady, Z and Huber, K 2015. Effects of oral butyrate application on insulin signaling in various tissues of chickens. Domestic Animal Endocrinology 50, 2631.
Mena, J, Manosalva, C, Ramirez, R, Chandia, L, Carroza, D, Loaiza, A, Burgos, RA and Hidalgo, MA 2013. Linoleic acid increases adhesion, chemotaxis, granule release, intracellular calcium mobilisation, MAPK phosphorylation and gene expression in bovine neutrophils. Veterinary Immunology and Immunopathology 151, 275284.
Meslin, C, Desert, C, Callebaut, I, Djari, A, Klopp, C, Pitel, F, Leroux, S, Martin, P, Froment, P, Guilbert, E, Gondret, F, Lagarrigue, S and Monget, P 2015. Expanding duplication of free fatty acid receptor-2 (GPR43) genes in the chicken genome. Genome Biology and Evolution 7, 13321348.
Morland, C, Lauritzen, KH, Puchades, M, Holm-Hansen, S, Andersson, K, Gjedde, A, Attramadal, H, Storm-Mathisen, J and Bergersen, LH 2015. The lactate receptor, G-protein-coupled receptor 81/hydroxycarboxylic acid receptor 1: expression and action in brain. Journal of Neuroscience Research 93, 10451055.
Nohr, MK, Pedersen, MH, Gille, A, Egerod, KL, Engelstoft, MS, Husted, AS, Sichlau, RM, Grunddal, KV, Poulsen, SS, Han, S, Jones, RM, Offermanns, S and Schwartz, TW 2013. GPR41/FFAR3 and GPR43/FFAR2 as cosensors for short-chain fatty acids in enteroendocrine cells vs FFAR3 in enteric neurons and FFAR2 in enteric leukocytes. Endocrinology 154, 35523564.
Ou, HY, Wu, HT, Lu, FH, Su, YC, Hung, HC, Wu, JS, Yang, YC, Wu, CL and Chang, CJ 2014. Activation of free fatty acid receptor 1 improves hepatic steatosis through a p38-dependent pathway. Journal of Molecular Endocrinology 53, 165174.
Psichas, A, Sleeth, ML, Murphy, KG, Brooks, L, Bewick, GA, Hanyaloglu, AC, Ghatei, MA, Bloom, SR and Frost, G 2015. The short chain fatty acid propionate stimulates GLP-1 and PYY secretion via free fatty acid receptor 2 in rodents. International Journal of Obesity (Lond) 39, 424429.
Puhl, HL 3rd, Won, YJ, Lu, VB and Ikeda, SR 2015. Human GPR42 is a transcribed multisite variant that exhibits copy number polymorphism and is functional when heterologously expressed. Scientific Reports 5, 12880.
Sakurai, T, Davenport, R, Stafford, S, Grosse, J, Ogawa, K, Cameron, J, Parton, L, Sykes, A, Mack, S, Bousba, S, Parmar, A, Harrison, D, Dickson, L, Leveridge, M, Matsui, J and Barnes, M 2014. Identification of a novel GPR81-selective agonist that suppresses lipolysis in mice without cutaneous flushing. European Journal of Pharmacology 727, 17.
Singh, N, Gurav, A, Sivaprakasam, S, Brady, E, Padia, R, Shi, H, Thangaraju, M, Prasad, PD, Manicassamy, S, Munn, DH, Lee, JR, Offermanns, S and Ganapathy, V 2014. Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. Immunity 40, 128139.
Song, T, Peng, J, Ren, J, Wei, HK and Peng, J 2015. Cloning and characterization of spliced variants of the porcine G protein coupled receptor 120. BioMed Research International 2015, 813816.
Svendsen, B, Pedersen, J, Albrechtsen, NJ, Hartmann, B, Torang, S, Rehfeld, JF, Poulsen, SS and Holst, JJ 2015. An analysis of cosecretion and coexpression of gut hormones from male rat proximal and distal small intestine. Endocrinology 156, 847857.
Tang, C, Ahmed, K, Gille, A, Lu, S, Grone, HJ, Tunaru, S and Offermanns, S 2015. Loss of FFA2 and FFA3 increases insulin secretion and improves glucose tolerance in type 2 diabetes. Nature Medicine 21, 173177.
Vancleef, L, Van Den Broeck, T, Thijs, T, Steensels, S, Briand, L, Tack, J and Depoortere, I 2015. Chemosensory signalling pathways involved in sensing of amino acids by the ghrelin cell. Scientific Reports 5, 15725.
van der Krieken, SE, Popeijus, HE, Mensink, RP and Plat, J 2015. CCAAT/enhancer binding protein beta in relation to ER stress, inflammation, and metabolic disturbances. BioMed Research International 2015, 324815.
van der Wielen, N, van Avesaat, M, de Wit, NJ, Vogels, JT, Troost, F, Masclee, A, Koopmans, SJ, van der Meulen, J, Boekschoten, MV, Muller, M, Hendriks, HF, Witkamp, RF and Meijerink, J 2014. Cross-species comparison of genes related to nutrient sensing mechanisms expressed along the intestine. PLoS ONE 9, e107531.
Weber, M, Locher, L, Huber, K, Kenez, A, Rehage, J, Tienken, R, Meyer, U, Danicke, S, Sauerwein, H and Mielenz, M 2016b. Longitudinal changes in adipose tissue of dairy cows from late pregnancy to lactation. Part 1: the adipokines apelin and resistin and their relationship to receptors linked with lipolysis. Journal of Dairy Science 99, 15491559.
Weber, M, Locher, L, Huber, K, Rehage, J, Tienken, R, Meyer, U, Danicke, S, Webb, L, Sauerwein, H and Mielenz, M 2016a. Longitudinal changes in adipose tissue of dairy cows from late pregnancy to lactation. Part 2: the SIRT-PPARGC1A axis and its relationship with the adiponectin system. Journal of Dairy Science 99, 15601570.
Yan, H and Ajuwon, KM 2015. Mechanism of butyrate stimulation of triglyceride storage and adipokine expression during adipogenic differentiation of porcine stromovascular cells. PLoS ONE 10, e0145940.
Zhang, J, Cheng, S, Wang, Y, Yu, X and Li, J 2014. Identification and characterization of the free fatty acid receptor 2 (FFA2) and a novel functional FFA2-like receptor (FFA2L) for short-chain fatty acids in pigs: evidence for the existence of a duplicated FFA2 gene (FFA2L) in some mammalian species. Domestic Animal Endocrinology 47, 108118.
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