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Farnesoid X receptor regulates PI3K/AKT/mTOR signaling pathway, lipid metabolism, and immune response in hybrid grouper

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Abstract

Some diseases related to lipid metabolism increase yearly in cultured fish, and the farnesoid X receptor (FXR) is a nuclear protein that plays a key role in inflammatory responses and lipid metabolism. However, the roles of FXR in hybrid grouper (Epinephelus fuscoguttatus♀ × E. lanceolatus♂) remain poorly understood. The main objective of this study was to explore the roles of hepatic FXR in triggering the immune response and the potential functions of FXR in regulating the lipid metabolism. In the present study, the full-length sequence of fxr from hybrid grouper was cloned and characterized for the first time. Upon the Vibrio parahaemolyticus stimulation, the transcriptional level of fxr was rapidly elevated in the head kidney tissue in the early stage of infection. In vivo and vitro, activation of FXR by obeticholic acid (OA) significantly increased the concentrations and mRNA levels of hepatic inflammatory cytokines. These effects were inversed when FXR was inhibited by guggulsterone (GU). Moreover, the activation of FXR to suppress the PI3K/AKT/mTOR signaling pathway improves hepatic lipid metabolism and reduces hepatic lipid accumulation in vivo and vitro. In addition, the inhibition of FXR activated the PI3K/AKT/mTOR pathway, decreased the lipolysis and increased the lipogenesis, and subsequently increased the lipid accumulation in fish. These results revealed the positive roles of FXR in triggering immune responses and improving lipid metabolism and accumulation in hybrid grouper.

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Abbreviations

3-pdk1:

3-Phosphoinositide dependent kinase-1

6pgd:

6-Phosphogluconate dehydrogenase

acc:

Acetyl-CoA carboxylase

AKT:

Serine/threonine-protein kinase

atgl:

Adipose triglyceride lipase

cpt1:

Carnitine palmitoyltransferase 1

deptor:

DEP domain-containing mTOR-interacting protein

dgka:

Diacylglycerol kinase alpha

fas:

Fatty acid synthase

FXR:

Farnesoid X receptor

g6pd:

Glucose 6-phosphate dehydrogenase

GU:

Guggulsterone

hl:

Hepatic lipase

hsl:

Hormone-sensitive lipase

lxr:

Liver X receptor alpha

me:

Malic enzyme

mlst8:

Target of rapamycin complex subunit lst 8

il1β:

Interleukin 1β

mTORC1:

Mammalian target of rapamycin complex 1

OA:

Obeticholic acid

PI3K:

Phosphatidylinositol 3-kinase

pi3k-rs5:

Phosphatidylinositol 3-kinase regulatory subunit 5

pras40:

Proline-rich Akt1 substrate 1

prr5:

Proline-rich protein 5

pparα:

Peroxisome proliferator-activated receptor alpha

PPARγ:

Peroxisome proliferator-activated receptor-gamma

raptor:

Regulatory associated protein of mTOR

RHEB:

Ras homolog enriched in brain

RICTOR:

Rapamycin-insensitive companion of mTOR

SIN1:

Target of rapamycin complex 2 subunit

SREBP1:

Sterol-regulator element-binding protein 1

tel:

Telomere length regulation protein

TG:

Triglycerides

tsc1:

Tuberous 1

tnfα:

Tumor necrosis factor-alpha

References

  • Chao L, Zhe Z, Qing-heng W, Rong-lian H, Yue-Wen D, Jun-hui L (2017) Molecular characterization and expression analysis of Pm-ApoL2 gene from Pinctada fucata martensii. J Guangdong Ocean Univ 37(3):7

    Google Scholar 

  • Chen Q, Liu H, Tan B, Dong X, Chi S, Yang Q, Zhang S (2016) Effects of dietary cholesterol level on growth performance, blood biochemical parameters and lipid metabolism of juvenile cobia (Rachycentron canadum). J Guangdong Ocean Univ 36(1):35–43

    Google Scholar 

  • Claudel T, Inoue Y, Barbier O, Duran-Sandoval D, Kosykh V, Fruchart J, Fruchart JC, Gonzalez FJ, Staels B (2003) Farnesoid X receptor agonists suppress hepatic apolipoprotein CIII expression. Gastroenterology 125(2):544–555. https://doi.org/10.1016/s0016-5085(03)00896-5

    Article  CAS  PubMed  Google Scholar 

  • Czaja MJ, Ding WX, Donohue TM Jr, Friedman SL, Kim JS, Komatsu M, Lemasters JJ, Lemoine A, Lin JD, Ou JH, Perlmutter DH, Randall G, Ray RB, Tsung A, Yin XM (2013) Functions of autophagy in normal and diseased liver. Autophagy 9(8):1131–1158. https://doi.org/10.4161/auto.25063

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Du J, Chen Q, Li Y, Xiang X, Xu W, Mai K, Ai Q (2020) Activation of the farnesoid X receptor (FXR) suppresses linoleic acid-induced inflammation in the large yellow croaker (Larimichthys crocea). J Nutr 150(9):2469–2477. https://doi.org/10.1093/jn/nxaa185

    Article  PubMed  Google Scholar 

  • Du J, Xiang X, Li Y, Ji R, Xu H, Mai K, Ai Q (2018) Molecular cloning and characterization of farnesoid X receptor from large yellow croaker (Larimichthys crocea) and the effect of dietary CDCA on the expression of inflammatory genes in intestine and spleen. Comp Biochem Physiol B Biochem Mol Biol 216:10–17. https://doi.org/10.1016/j.cbpb.2017.09.007

    Article  CAS  PubMed  Google Scholar 

  • Fiorucci S, Rizzo G, Donini A, Distrutti E, Santucci L (2007) Targeting farnesoid X receptor for liver and metabolic disorders. Trends Mol Med 13(7):298–309. https://doi.org/10.1016/j.molmed.2007.06.001

    Article  CAS  PubMed  Google Scholar 

  • Fuentes EN, Björnsson BT, Valdés JA, Einarsdottir IE, Lorca B, Alvarez M, Molina A (2011) IGF-I/PI3K/Akt and IGF-I/MAPK/ERK pathways in vivo in skeletal muscle are regulated by nutrition and contribute to somatic growth in the fine flounder. Am J Physiol Regul Integr Comp Physiol 300(6):R1532–R1542

    Article  CAS  PubMed  Google Scholar 

  • Gai Z, Visentin M, Gui T, Zhao L, Thasler WE, Hausler S, Hartling I, Cremonesi A, Hiller C, Kullak-Ublick GA (2018) Effects of farnesoid X receptor activation on arachidonic acid metabolism, NF-kB signaling, and sepatic inflammation. Mol Pharmacol 94(2):802–811. https://doi.org/10.1124/mol.117.111047

    Article  CAS  PubMed  Google Scholar 

  • Gamper CJ, Powell JD (2012) All PI3Kinase signaling is not mTOR: dissecting mTOR-dependent and independent signaling pathways in T cells. Front Immunol 3:312

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gui L, Mai H, Chi S, Zhou W, Li Y, Tan B (2019) Effects of yeast culture on growth performance, hematological parameters, immunity and disease resistance of Litopenaeus vannamei. J Guangdong Ocean Univ 39(3):30–37

    Google Scholar 

  • Hagiwara A, Cornu M, Cybulski N, Polak P, Betz C, Trapani F, Terracciano L, Heim MH, Rüegg MA, Hall MN (2012) Hepatic mTORC2 activates glycolysis and lipogenesis through Akt, glucokinase, and SREBP1c. Cell Metab 15(5):725–738

    Article  CAS  PubMed  Google Scholar 

  • He Y, Ye G, Chi S, Tan B, Dong X, Yang Q, Liu H, Zhang S (2020) Integrative transcriptomic and small RNA sequencing reveals immune-related miRNA-mRNA regulation network for soybean meal-induced enteritis in hybrid grouper, Epinephelus fuscoguttatusfemale symbol x Epinephelus lanceolatusmale symbol. Front Immunol 11:1502. https://doi.org/10.3389/fimmu.2020.01502

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hirschfield GM, Mason A, Luketic V, Lindor K, Gordon SC, Mayo M, Kowdley KV, Vincent C, Bodhenheimer HC Jr, Pares A, Trauner M, Marschall HU, Adorini L, Sciacca C, Beecher-Jones T, Castelloe E, Bohm O, Shapiro D (2015) Efficacy of obeticholic acid in patients with primary biliary cirrhosis and inadequate response to ursodeoxycholic acid. Gastroenterology 148(4):751-761 e758. https://doi.org/10.1053/j.gastro.2014.12.005

    Article  CAS  PubMed  Google Scholar 

  • Hong-yu L, Li-xian L, Stephen A, Ze T, Wei F, Bei-ping T, Xiao-hui D, Shu-yan C, Qi-hui Y, Shuang Z, Wen-hao Z (2021) Effects of dietary yeast culture supplementation on growth, intestinal morphology, immunity, and disease resistance in Epinephelus fuscoguttatus♀× Epinephelus lanceolatu♂. J Guangdong Ocean Univ 41(3):11

    Google Scholar 

  • Hortsch SK, Kremling A (2018) Characterization of noise in multistable genetic circuits reveals ways to modulate heterogeneity. PLoS ONE 13(3):e0194779

    Article  PubMed  PubMed Central  Google Scholar 

  • Howarth DL, Hagey LR, Law SH, Ai N, Krasowski MD, Ekins S, Moore JT, Kollitz EM, Hinton DE, Kullman SW (2010) Two farnesoid X receptor alpha isoforms in Japanese medaka (Oryzias latipes) are differentially activated in vitro. Aquat Toxicol 98(3):245–255

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang F, Zheng X, Ma X, Jiang R, Zhou W, Zhou S, Zhang Y, Lei S, Wang S, Kuang J, Han X, Wei M, You Y, Li M, Li Y, Liang D, Liu J, Chen T, Yan C, Wei R, Rajani C, Shen C, Xie G, Bian Z, Li H, Zhao A, Jia W (2019) Theabrownin from Pu-erh tea attenuates hypercholesterolemia via modulation of gut microbiota and bile acid metabolism. Nat Commun 10(1):4971. https://doi.org/10.1038/s41467-019-12896-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Iracheta-Vellve A, Calenda CD, Petrasek J, Ambade A, Kodys K, Adorini L, Szabo G (2018) FXR and TGR5 agonists ameliorate liver injury, steatosis, and inflammation after binge or prolonged alcohol feeding in mice. Hepatol Commun 2(11):1379–1391. https://doi.org/10.1002/hep4.1256

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jadhav K, Xu Y, Xu Y, Li Y, Xu J, Zhu Y, Adorini L, Lee YK, Kasumov T, Yin L, Zhang Y (2018) Reversal of metabolic disorders by pharmacological activation of bile acid receptors TGR5 and FXR. Mol Metab 9:131–140. https://doi.org/10.1016/j.molmet.2018.01.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ji K, Liang H, Ren M, Ge X, Mi H, Pan L, Yu H (2020) The immunoreaction and antioxidant capacity of juvenile blunt snout bream (Megalobrama amblycephala) involves the PI3K/Akt/Nrf2 and NF-kappaB signal pathways in response to dietary methionine levels. Fish Shellfish Immunol 105:126–134. https://doi.org/10.1016/j.fsi.2020.07.005

    Article  CAS  PubMed  Google Scholar 

  • Jia W, Xie G, Jia W (2018) Bile acid-microbiota crosstalk in gastrointestinal inflammation and carcinogenesis. Nat Rev Gastroenterol Hepatol 15(2):111–128. https://doi.org/10.1038/nrgastro.2017.119

    Article  CAS  PubMed  Google Scholar 

  • Jiang C, Xie C, Li F, Zhang L, Nichols RG, Krausz KW, Cai J, Qi Y, Fang ZZ, Takahashi S, Tanaka N, Desai D, Amin SG, Albert I, Patterson AD, Gonzalez FJ (2015) Intestinal farnesoid X receptor signaling promotes nonalcoholic fatty liver disease. J Clin Invest 125(1):386–402. https://doi.org/10.1172/JCI76738

    Article  PubMed  Google Scholar 

  • Jung K, Kim M, So J, Lee SH, Ko S, Shin D (2021) Farnesoid X receptor activation impairs liver progenitor cell–mediated liver regeneration via the PTEN-PI3K-AKT-mTOR Axis in zebrafish. J Hepatology 74(1):397–410

    Article  CAS  Google Scholar 

  • Kim K, Qiang L, Hayden MS, Sparling DP, Purcell NH, Pajvani UB (2016) mTORC1-independent raptor prevents hepatic steatosis by stabilizing PHLPP2. Nat Commun 7(1):10255. https://doi.org/10.1038/ncomms10255

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li Z, Xu G, Qin Y, Zhang C, Tang H, Yin Y, Xiang X, Li Y, Zhao J, Mulholland M (2014) Ghrelin promotes hepatic lipogenesis by activation of mTOR-PPARγ signaling pathway. Proc Natl Acad Sci 111(36):13163–13168

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liang H, Huang D, Wu Y, Wang C, Zhong W (2013) Effects of temperature and salinity on survival and food intake of grouper hybrid (Epinephelus lanceolatus♂× E fuscoguttatus♀). J Guangdong Ocean Univ 33(4):22–26

    Google Scholar 

  • Liu DD, Han CC, Wan HF, He F, Xu HY, Wei SH, Du XH, Xu F (2016) Effects of inhibiting PI3K-Akt-mTOR pathway on lipid metabolism homeostasis in goose primary hepatocytes. Animal 10(8):1319–1327. https://doi.org/10.1017/S1751731116000380

    Article  CAS  PubMed  Google Scholar 

  • Mao Z, Zhang W (2018) Role of mTOR in glucose and lipid metabolism. Int J Mol Sci 19(7):2043. https://doi.org/10.3390/ijms19072043

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pasquier J, Cabau C, Nguyen T, Jouanno E, Severac D, Braasch I, Journot L, Pontarotti P, Klopp C, Postlethwait JH (2016) Gene evolution and gene expression after whole genome duplication in fish: the PhyloFish database. BMC Genom 17(1):1–10

    Article  Google Scholar 

  • Pineda Torra IS, Claudel T, Duval C, Kosykh V, Fruchart J-C, Staels B (2003) Bile acids induce the expression of the human peroxisome proliferator-activated receptor α gene via activation of the farnesoid X receptor. J Molec Endocrinol 17(2):259–272

    Article  Google Scholar 

  • Rahimnejad S, Bang IC, Park J-Y, Sade A, Choi J, Lee S-MJA (2015) Effects of dietary protein and lipid levels on growth performance, feed utilization and body composition of juvenile hybrid grouper, Epinephelus fuscoguttatus × E. lanceolatus. Aquaculture 446:283–289

    Article  CAS  Google Scholar 

  • Ricoult SJ, Yecies JL, Ben-Sahra I, Manning BD (2016) Oncogenic PI3K and K-Ras stimulate de novo lipid synthesis through mTORC1 and SREBP. Oncogene 35(10):1250–1260. https://doi.org/10.1038/onc.2015.179

    Article  CAS  PubMed  Google Scholar 

  • Ryan KK, Tremaroli V, Clemmensen C, Kovatcheva-Datchary P, Myronovych A, Karns R, Wilson-Perez HE, Sandoval DA, Kohli R, Backhed F, Seeley RJ (2014) FXR is a molecular target for the effects of vertical sleeve gastrectomy. Nature 509(7499):183–188. https://doi.org/10.1038/nature13135

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Saxton RA, Sabatini DM (2017) mTOR signaling in growth, metabolism, and disease. Cell 168(6):960–976. https://doi.org/10.1016/j.cell.2017.02.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schmitt J, Kong B, Stieger B, Tschopp O, Schultze SM, Rau M, Weber A, Mullhaupt B, Guo GL, Geier A (2015) Protective effects of farnesoid X receptor (FXR) on hepatic lipid accumulation are mediated by hepatic FXR and independent of intestinal FGF15 signal. Liver Int 35(4):1133–1144. https://doi.org/10.1111/liv.12456

    Article  CAS  PubMed  Google Scholar 

  • Schneider KM, Albers S, Trautwein C (2018) Role of bile acids in the gut-liver axis. J Hepatol 68(5):1083–1085. https://doi.org/10.1016/j.jhep.2017.11.025

    Article  PubMed  Google Scholar 

  • Sengupta S, Peterson TR, Laplante M, Oh S, Sabatini DM (2010) mTORC1 controls fasting-induced ketogenesis and its modulation by ageing. Nature 468(7327):1100–1104. https://doi.org/10.1038/nature09584

    Article  CAS  PubMed  Google Scholar 

  • Shaik FB, Prasad DV, Narala VR (2015) Role of farnesoid X receptor in inflammation and resolution. Inflamm Res 64(1):9–20. https://doi.org/10.1007/s00011-014-0780-y

    Article  CAS  PubMed  Google Scholar 

  • Shao-hong M, Yu-chong H, Ji-chang J, Shuang-hu C (2019) Cloning and Prokaryotic Expression of PspF Gene from Vibrio Harveyi. J Guangdong Ocean Univ 39(5):1–7

    Google Scholar 

  • Sinal CJ, Tohkin M, Miyata M, Ward JM, Lambert G, Gonzalez FJ (2000) Targeted disruption of the nuclear receptor FXR/BAR impairs bile acid and lipid homeostasis. Cell 102(6):731–744. https://doi.org/10.1016/s0092-8674(00)00062-3

    Article  CAS  PubMed  Google Scholar 

  • Tian J-J, Jin Y-Q, Yu E-M, Sun J-H, Xia Y, Zhang K, Li Z-F, Gong W-B, Wang G-J, Xie J (2021) Farnesoid X receptor is an effective target for modulating lipid accumulation in grass carp Ctenopharyngodon Idella. Aquaculture 534:736248. https://doi.org/10.1016/j.aquaculture.2020.736248

    Article  CAS  Google Scholar 

  • Wagner EF, Eferl R (2005) Fos/AP-1 proteins in bone and the immune system. J Immunol Rev 208(1):126–140

    Article  CAS  Google Scholar 

  • Wahlstrom A, Sayin SI, Marschall HU, Backhed F (2016) Intestinal crosstalk between bile acids and microbiota and its impact on host metabolism. Cell Metab 24(1):41–50. https://doi.org/10.1016/j.cmet.2016.05.005

    Article  CAS  PubMed  Google Scholar 

  • Wang A, Yang Q, Tan B, Xiao W, Jia J, Dong X, Zhang S (2018) Effects of enzymolytic soybean meal on growth performance, serum biochemical indices, non-specific immunity and disease resistance of juvenile Litopenaeus vannamei. J Guangdong Ocean Univ 38(1):14–21

    Google Scholar 

  • Watanabe M, Houten SM, Wang L, Moschetta A, Mangelsdorf DJ, Heyman RA, Moore DD, Auwerx J (2004) Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c. J Clin Invest 113(10):1408–1418. https://doi.org/10.1172/JCI21025

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu K, Zhao T, Hogstrand C, Xu YC, Ling SC, Chen GH, Luo Z (2020) FXR-mediated inhibition of autophagy contributes to FA-induced TG accumulation and accordingly reduces FA-induced lipotoxicity. Cell Commun Signal 18(1):47. https://doi.org/10.1186/s12964-020-0525-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xie J, Qiu D, Liu C, Zhu W, Zeng L (2013) Effcets of Vibrio alginolyticus peptidoglycan on astaxanthin Level, immune indicators and protection in Litopenaeus vannamei. J Guangdong Ocean Univ 33(01):50–55

    CAS  Google Scholar 

  • Xiu-ping F, Xiao-ming Q, Chao-hua Z, Jian-ping C, Qian-feng Z (2018) Nutritional and volatile flavor components of dorsal and ventral muscle from hybrid grouper (Epinephelus fuscoguttatus♀ × E. lanceolatus♂). J Guangdong Ocean Univ 38(1):8

    Google Scholar 

  • Xu J, Li X, Yao X, Xie S, Chi S, Zhang S, Cao J, Tan B (2022a) Protective effects of bile acids against hepatic lipid accumulation in hybrid grouper fed a high-lipid diet. Front Nutr 9:813249. https://doi.org/10.3389/fnut.2022.813249

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu J, Xie S, Chi S, Zhang S, Cao J, Tan B (2022b) Protective effects of taurocholic acid on excessive hepatic lipid accumulation via regulation of bile acid metabolism in grouper. Food Funct 13(5):3050–3062

    Article  CAS  PubMed  Google Scholar 

  • Xu J, Xie S, Chi S, Zhang S, Cao J, Tan B (2022c) Short-term dietary antibiotics altered the intestinal microbiota and improved the lipid metabolism in hybrid grouper fed medium and high-lipid diets. Aquaculture 547:737453. https://doi.org/10.1016/j.aquaculture.2021.737453

    Article  CAS  Google Scholar 

  • Xu P, Xu K, Wang J, Jiang JP, Chen LQ (2011) Pioglitazone: a promising therapeutic tool in sodium taurocholate-induced severe acute pancreatitis. Dig Dis Sci 56(4):1082–1089. https://doi.org/10.1007/s10620-010-1393-0

    Article  CAS  PubMed  Google Scholar 

  • Yamauchi Y, Furukawa K, Hamamura K, Furukawa K (2011) Positive feedback loop between PI3K-Akt-mTORC1 signaling and the lipogenic pathway boosts Akt signaling: induction of the lipogenic pathway by a melanoma antigen. Cancer Res 71(14):4989–4997. https://doi.org/10.1158/0008-5472.CAN-10-4108

    Article  CAS  PubMed  Google Scholar 

  • Zhang S, Wang J, Liu Q, Harnish DC (2009) Farnesoid X receptor agonist WAY-362450 attenuates liver inflammation and fibrosis in murine model of non-alcoholic steatohepatitis. J Hepatol 51(2):380–388. https://doi.org/10.1016/j.jhep.2009.03.025

    Article  CAS  PubMed  Google Scholar 

  • Zhang Y, Lee FY, Barrera G, Lee H, Vales C, Gonzalez FJ, Willson TM, Edwards PA (2006) Activation of the nuclear receptor FXR improves hyperglycemia and hyperlipidemia in diabetic mice. Proc Natl Acad Sci U S A 103(4):1006–1011. https://doi.org/10.1073/pnas.0506982103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhi-xin W, Hai-ying L, Xiao-dong D, Rong-lian H, Yue-wen D, Qing-heng W, Yu J (2013) Cloning and express characters of HSP60 gene from Pinctada martensii. J Guangdong Ocean Univ 33(006):14–23

    Google Scholar 

  • Zhu S, Xiang X, Xu X, Gao S, Mai K, Ai Q (2019) TIR domain-containing adaptor-inducing interferon-beta (TRIF) participates in antiviral immune responses and hepatic lipogenesis of large yellow croaker (Larimichthys Crocea). Front Immunol 10:2506. https://doi.org/10.3389/fimmu.2019.02506

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhu W, Qiu D, Gan Z, Lu Y, Jian J (2015) Antivirus effects of Vibrio alginolyticus peptidoglycan on Litopenaeus vannamei against white spot syndrome virus. J Guangdong Ocean Univ 35(6):40–46

    Google Scholar 

  • Zhu Y, Li F, Guo GL (2011) Tissue-specific function of farnesoid X receptor in liver and intestine. Pharmacol Res 63(4):259–265. https://doi.org/10.1016/j.phrs.2010.12.018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We sincerely thank Xiaohui Dong, Hongyu Liu, and Qihui Yang (Laboratory of Aquatic Animal Nutrition and Feed of Fisheries College of the Guangdong Ocean University of Zhanjiang in China) for providing methodological help during the experiments and proofreading the article.

Funding

This work was supported by the National Key R&D Program of China [2019YFD0900200], the China Agriculture Research System of MOF and MARA [CARS-47], the Science and Technology Project of Zhanjiang [2020A05003], the National Natural Science Foundation of China [no. 31772864], and the Natural Science Foundation of Guangdong Province [2018A030313154&2020A1515011129].

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Authors and Affiliations

  1. Laboratory of Aquatic Animal Nutrition and Feed, Fisheries College, Guangdong Ocean University, Zhanjiang, 524088, China

    Jia Xu, Xinzhou Yao, Xiaoyue Li, Shiwei Xie, Shuyan Chi, Shuang Zhang, Junming Cao & Beiping Tan

  2. Aquatic Animals Precision Nutrition and High Efficiency Feed Engineering Research Center of Guangdong Province, Zhanjiang, China

    Shiwei Xie, Shuyan Chi, Shuang Zhang, Junming Cao & Beiping Tan

  3. Key Laboratory of Aquatic, Livestock and Poultry Feed Science and Technology in South China, Ministry of Agriculture, Zhanjiang, China

    Shiwei Xie, Shuyan Chi, Shuang Zhang, Junming Cao & Beiping Tan

  4. Guangdong Provincial Key Lab of Pathogenic Biology and Epidemiology for Aquatic Economic Animals, Zhanjiang, China

    Shiwei Xie

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  1. Jia Xu
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Contributions

Jia Xu conducted the methodology, formal analysis, investigation, data curation, and writing—original draft; Xinzhou Yao conducted the data curation, investigation, and writing—original draft; Xiaoyue Li conducted the investigation, data curation, and visualization; Shiwei Xie conducted the conceptualization, resources, and visualization; Shuyan Chi conducted the methodology and conceptualization; Shuang Zhang conducted the conceptualization and funding acquisition; Junming Cao conducted the methodology, conceptualization, and funding acquisition; and Beiping Tan conducted the methodology, conceptualization, writing—review and editing, and funding acquisition. All authors read and approved the final manuscript.

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Correspondence to Shiwei Xie or Beiping Tan.

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The experimental procedures were approved by the Animal Ethical and Welfare Committee of Guangdong Ocean University (Guangdong, China), processing ID: GDOU-AEWC-20180063.

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Highlights

• The full-length sequence of fxr from hybrid grouper was cloned for the first time.

• Tnhibition of FXR decreased the expression of inflammatory cytokines.

• Activation of hepatic FXR improved the lipid accumulation and metabolism.

• Inhibition of FXR activated the PI3K/AKT/mTOR pathway in vivo and vitro.

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Xu, J., Yao, X., Li, X. et al. Farnesoid X receptor regulates PI3K/AKT/mTOR signaling pathway, lipid metabolism, and immune response in hybrid grouper. Fish Physiol Biochem 48, 1521–1538 (2022). https://doi.org/10.1007/s10695-022-01130-z

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