脂联素及其受体激动剂在禽脂肪性肝病中的应用展望

doi:10.16431/j.cnki.1671-7236.2022.02.036

Abstract

Abstract: Adiponectin is a hormone that can participate in the regulation of glucose and lipid metabolism, energy regulation, immune response, resistance to inflammation, oxidative stress and apoptosis.Avian fatty liver disease is lipid metabolism disorder, hepatocyte steatosis and inflammatory reaction caused by abnormal lipid metabolic pathways such as fatty acid synthesis and esterification, fatty acid transport, fatty acid oxidation, lipolysis and utilization in avian liver.This paper introduces adiponectin and its molecular structure, adiponectin receptor and its involved signal pathways, and focuses on the regulatory role and mechanism of adiponectin on liver lipid metabolism, inflammation, oxidative stress, hepatocyte apoptosis and autophagy, as well as the physiological role of adiponectin receptor agonists.At the same time, combined with the occurrence and development mechanism of avian fatty liver disease, the application prospect of adiponectin and its receptor agonists was prospected.This article provides a new idea for the prevention and treatment of fatty liver disease in poultry and even other animals.

Key words: adiponectin; adiponectin receptor agonists; liver; avian; fatty liver disease

CLC Number:

S852

CUI Chengyu, MA Ben, ZHAO Jiahui, ZHAO Zijuan, CHEN Yu, CAO Zhongzan, LUAN Xinhong. Application Prospect of Adiponectin and Its Receptor Agonists in Avian Fatty Liver Disease[J]. China Animal Husbandry & Veterinary Medicine, 2022, 49(2): 738-745.

References

[1] FANG H, JUDD R L. Adiponectin regulation and function[J]. Comprehensive Physiology, 2018, 8(3): 1031-1063.
[2] BROCHU-GAUDREAU K, REHFELDT C, BLOUIN R, et al. Adiponectin action from head to toe[J]. Endocrine, 2010, 37(1): 11-32.
[3] MADDINENI S. Adiponectin gene is expressed in multiple tissues in the chicken: Food deprivation influences adiponectin messenger ribonucleic acid expression[J]. Endocrinology, 2005, 146(10): 4250-4256.
[4] CAO Z, LI J, LUO L, et al. Molecular cloning and expression analysis of adiponectin and its receptors (AdipoR1 and AdipoR2) in the hypothalamus of the Huoyan goose during different stages of the egg-laying cycle[J]. Reproductive Biology and Endocrinology, 2015, 13: 87.
[5] FRIZZELL N, RAJESH M, JEPSON M J, et al. Succination of thiol groups in adipose tissue proteins in diabetes: Succination inhibits polymerization and secretion of adiponectin[J]. Journal of Biological Chemistry, 2009, 284(38): 25772-25781.
[6] SHAPIRO L, SCHERER P E. The crystal structure of a complement-1q family protein suggests an evolutionary link to tumor necrosis factor[J]. Current Biology, 1998, 8(6): 335-338.
[7] WAKI H, YAMAUCHI T, KAMON J, et al. Impaired multimerization of human adiponectin mutants associated with diabetes. Molecular structure and multimer formation of adiponectin[J]. Journal of Biological Chemistry, 2003, 278(41): 40352-40363.
[8] HARA K, HORIKOSHI M, YAMAUCHI T, et al. Measurement of the high-molecular weight form of adiponectin in plasma is useful for the prediction of insulin resistance and metabolic syndrome[J]. Diabetes Care, 2006, 29(6): 1357-1362.
[9] YAMAUCHI T, KAMON J, ITO Y, et al. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects[J]. Nature, 2003, 423(6941): 762-769.
[10] MAO X, KIKANI C K, RIOJAS R A, et al. APPL1 binds to adiponectin receptors and mediates adiponectin signalling and function[J]. Nature Cell Biology, 2006, 8(5): 516-523.
[11] HOLLAND W L, MILLER R A, WANG Z V, et al. Receptor-mediated activation of ceramidase activity initiates the pleiotropic actions of adiponectin[J]. Nature Medicine, 2011, 17(1): 55-63.
[12] WEI R, HAN C, DENG D, et al. Research progress into the physiological changes in metabolic pathways in waterfowl with hepatic steatosis[J]. British Poultry Science, 2021, 62(1): 118-124.
[13] SANDERS F W, GRIFFIN J L. De novo lipogenesis in the liver in health and disease: More than just a shunting yard for glucose[J]. Biological Reviews of the Cambridge Philosophical Society, 2016, 91(2): 452-468.
[14] STRABLE M S, NTAMBI J M. Genetic control of de novo lipogenesis: Role in diet-induced obesity[J]. Critical Reviews in Biochemistry and Molecular Biology, 2010, 45(3): 199-214.
[15] STOECKMAN A K, TOWLE H C. The role of SREBP-1c in nutritional regulation of lipogenic enzyme gene expression[J]. Journal of Biological Chemistry, 2002, 277(30): 27029-27035.
[16] LI Y, XU S, MIHAYLOVA M M, et al. AMPK phosphorylates and inhibits SREBP activity to attenuate hepatic steatosis and atherosclerosis in diet-induced insulin-resistant mice[J]. Cell Metabolism, 2011, 13(4): 376-388.
[17] REDDY J K, RAO M S. Lipid metabolism and liver inflammation. Ⅱ. Fatty liver disease and fatty acid oxidation[J]. American Journal of Physiology-Gastrointestinal and Liver Physiology, 2006, 290(5): G852-858.
[18] POIRIER Y, ANTONENKOV V D, GLUMOFF T, et al. Peroxisomal beta-oxidation——A metabolic pathway with multiple functions[J]. Biochimica et Biophysica Acta, 2006, 1763(12): 1413-1426.
[19] MISRA P. AMP activated protein kinase: A next generation target for total metabolic control[J]. Expert Opinion on Therapeutic Targets, 2008, 12(1): 91-100.
[20] CHEN H, ZHANG L, LI X, et al. Adiponectin activates the AMPK signaling pathway to regulate lipid metabolism in bovine hepatocytes[J]. The Journal of Steroid Biochemistry and Molecular Biology, 2013, 138: 445-454.
[21] YAMAUCHI T, KAMON J, WAKI H, et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity[J]. Nature Medicine, 2001, 7(8): 941-946.
[22] YUAN M, KONSTANTOPOULOS N, LEE J, et al. Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkbeta[J]. Science, 2001, 293(5535): 1673-1677.
[23] FELDSTEIN A E, WERNEBURG N W, CANBAY A, et al. Free fatty acids promote hepatic lipotoxicity by stimulating TNF-alpha expression via a lysosomal pathway[J]. Hepatology, 2004, 40(1): 185-194.
[24] IVANOVSKA J, KANG N C, IVANOVSKI N, et al. Recombinant adiponectin protects the newborn rat lung from lipopolysaccharide-induced inflammatory injury[J]. Physiological Reports, 2020, 8(17): e14553.
[25] CHINETTI G, ZAWADSKI C, FRUCHART J C, et al. Expression of adiponectin receptors in human macrophages and regulation by agonists of the nuclear receptors PPARalpha, PPARgamma, and LXR[J]. Biochemical and Biophysical Research Communications, 2004, 314(1): 151-158.
[26] AJUWON K M, SPURLOCK M E. Adiponectin inhibits LPS-induced NF-kappaB activation and IL-6 production and increases PPARgamma2 expression in adipocytes[J]. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, 2005, 288(5): R1220-1225.
[27] WOLF A M, WOLF D, RUMPOLD H, et al. Adiponectin induces the anti-inflammatory cytokines IL-10 and IL-1RA in human leukocytes[J]. Biochemical and Biophysical Research Communications, 2004, 323(2): 630-635.
[28] HUANG H, PARK P H, MCMULLEN M R, et al. Mechanisms for the anti-inflammatory effects of adiponectin in macrophages[J]. Journal of Gastroenterology and Hepatology, 2008, 23 Suppl 1: S50-S53.
[29] MASAKI T, CHIBA S, TATSUKAWA H, et al. Adiponectin protects LPS-induced liver injury through modulation of TNF-alpha in KK-Ay obese mice[J]. Hepatology, 2004, 40(1): 177-184.
[30] XU A, WANG Y, KESHAW H, et al. The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice[J]. Journal of Clinical Investigation, 2003, 112(1): 91-100.
[31] KOBASHI C, URAKAZE M, KISHIDA M, et al. Adiponectin inhibits endothelial synthesis of interleukin-8[J]. Circulation Research, 2005, 97(12): 1245-1252.
[32] KADOWAKI T, YAMAUCHI T. Adiponectin and adiponectin receptors[J]. Endocrine Reviews, 2005, 26(3): 439-451.
[33] ENDO M, MASAKI T, SEIKE M, et al. TNF-alpha induces hepatic steatosis in mice by enhancing gene expression of sterol regulatory element binding protein-1c (SREBP-1c)[J]. Experimental Biology and Medicine, 2007, 232(5): 614-621.
[34] PASTORINO J G, SHULGA N. Tumor necrosis factor-alpha can provoke cleavage and activation of sterol regulatory element-binding protein in ethanol-exposed cells via a caspase-dependent pathway that is cholesterol insensitive[J]. Journal of Biological Chemistry, 2008, 283(37): 25638-25649.
[35] XING C, WANG Y, DAI X, et al. The protective effects of resveratrol on antioxidant function and the mRNA expression of inflammatory cytokines in the ovaries of hens with fatty liver hemorrhagic syndrome[J]. Poultry Science, 2020, 99(2): 1019-1027.
[36] YAMAUCHI T, NIO Y, MAKI T, et al. Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions[J]. Nature Medicine, 2007, 13(3): 332-339.
[37] IKEGAMI Y, INUKAI K, IMAI K, et al. Adiponectin upregulates ferritin heavy chain in skeletal muscle cells[J]. Diabetes, 2009, 58(1): 61-70.
[38] LI X, LI M R, GUO Z X. Effects of adiponectin on oxidative stress and apoptosis in human cardiac myocytes cultured with high glucose[J]. Chinese Medical Journal, 2012, 125(23): 4209-4213.
[39] REN Y, LI Y, YAN J, et al. Adiponectin modulates oxidative stress-induced mitophagy and protects C2C12 myoblasts against apoptosis[J]. Scientific Reports, 2017, 7(1): 3209.
[40] WANG B, GUO H, LI X, et al. Adiponectin attenuates oxygen-glucose deprivation-induced mitochondrial oxidative injury and apoptosis in hippocampal HT22 cells via the JAK2/STAT3 pathway[J]. Cell Transplantation, 2018, 27(12): 1731-1743.
[41] THAKUR V, PRITCHARD M T, MCMULLEN M R, et al. Adiponectin normalizes LPS-stimulated TNF-alpha production by rat Kupffer cells after chronic ethanol feeding[J]. American Journal of Physiology. Gastrointestinal and Liver Physiology, 2006, 290(5): G998-1007.
[42] KIM M J, NAGY L E, PARK P H. Globular adiponectin inhibits ethanol-induced reactive oxygen species production through modulation of NADPH oxidase in macrophages: Involvement of liver kinase B1/AMP-activated protein kinase pathway[J]. Molecular Pharmacology, 2014, 86(3): 284-296.
[43] WEI C D, LI Y, ZHENG H Y, et al. Globular adiponectin protects H9c2 cells from palmitate-induced apoptosis via Akt and ERK1/2 signaling pathways[J]. Lipids in Health and Disease, 2012, 11: 135.
[44] PARK P H, SANZ-GARCIA C, NAGY L E. Adiponectin as an anti-fibrotic and anti-inflammatory adipokine in the liver[J]. Current Pathobiology Reports, 2015, 3(4): 243-252.
[45] MAIURI M C, ZALCKVAR E, KIMCHI A, et al. Self-eating and self-killing: Crosstalk between autophagy and apoptosis[J]. Nature Reviews Molecular Cell Biology, 2007, 8(9): 741-752.
[46] YAN S, HUDA N, KHAMBU B, et al. Relevance of autophagy to fatty liver diseases and potential therapeuticapplications[J]. Amino Acids, 2017, 49(12): 1965-1979.
[47] ESSICK E E, WILSON R M, PIMENTEL D R, et al. Adiponectin modulates oxidative stress-induced autophagy in cardiomyocytes[J]. PLoS One, 2013, 8(7): e68697.
[48] GAMBERI T, MODESTI A, MAGHERINI F, et al. Activation of autophagy by globular adiponectin is required for muscle differentiation[J]. Biochimica et Biophysica Acta, 2016, 1863(4): 694-702.
[49] NEPAL S, KIM M J, LEE E S, et al. Modulation of Atg5 expression by globular adiponectin contributes to autophagy flux and suppression of ethanol-induced cell death in liver cells[J]. Food and Chemical Toxicology, 2014, 68: 11-22.
[50] NEPAL S, PARK P H. Activation of autophagy by globular adiponectin attenuates ethanol-induced apoptosis in HepG2 cells: Involvement of AMPK/FoxO3A axis[J]. Biochimica et Biophysica Acta, 2013, 1833(10): 2111-2125.
[51] WU X, QIU W, HU Z, et al. An adiponectin receptor agonist reduces type 2 diabetic periodontitis[J]. Journal of Dental Research, 2019, 98(3): 313-321.
[52] OKADA-IWABU M, YAMAUCHI T, IWABU M, et al. A small-molecule AdipoR agonist for type 2 diabetes and short life in obesity[J]. Nature, 2013, 503(7477): 493-499.
[53] ZHANG Y, ZHAO J, LI R, et al. AdipoRon, the first orally active adiponectin receptor activator, attenuates postischemic myocardial apoptosis through both AMPK-mediated and AMPK-independent signalings[J]. American Journal of Physiology. Endocrinology and Metabolism, 2015, 309(3): E275-E282.
[54] GU D, SHI Y, GONG Z, et al. AdipoRon, an adiponectin receptor agonist, protects contrast-induced nephropathy by suppressing oxidative stress and inflammation via activation of the AMPK pathway[J]. Clinical and Experimental Nephrology, 2020, 24(11): 989-998.
[55] ZATORSKI H, SALAGA M, ZIELI N ' SKA M, et al. AdipoRon, an orally active, synthetic agonist of AdipoR1 and AdipoR2 receptors has gastroprotective effect in experimentally induced gastric ulcers in mice[J]. Molecules, 2021, 26(10): 2946.
[56] XIAO W Z, ZHANG L. Adiponectin receptor agonist AdipoRon relieves endotoxin-induced acute hepatitis in mice[J]. Chinese Medical Journal, 2019, 132(20): 2438-2445.
[57] SHA M, GAO Y, DENG C, et al. Therapeutic effects of AdipoRon on liver inflammation and fibrosis induced by CCl₄ in mice[J]. International Immunopharmacology, 2020, 79: 106157.
[58] QIU W, WU H, HU Z, et al. Identification and characterization of a novel adiponectin receptor agonist adipo anti-inflammation agonist and its anti-inflammatory effects in vitro and in vivo[J]. British Journal of Pharmacology, 2021, 178(2): 280-297.
[59] SHI X, ZHU S, JIN H, et al. The anti-inflammatory effect of KS23, a novel peptide derived from globular adiponectin, on endotoxin-induced uveitis in rats[J]. Frontiers in Pharmacology, 2020, 11: 585446.
[60] OTVOS L J, HASPINGER E, LA RUSSA F, et al. Design and development of a peptide-based adiponectin receptor agonist for cancer treatment[J]. BMC Biotechnology, 2011, 11: 90.

Application Prospect of Adiponectin and Its Receptor Agonists in Avian Fatty Liver Disease

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	LU Meixi, LI Huihui, TANG Yi, LIANG Suyun, HOU Shuisheng. Effect of DHAV-3 Infection on the Bile Secretion Pathway in Ducklings of Different Ages [J]. China Animal Husbandry & Veterinary Medicine, 2025, 52(6): 2830-2838.
[2]	GUO Zikai, LUO Anqi, LI Weihan, LIU Juncheng, JIANG Tao, LIU Yisong. Study on the Mechanism of Action of Extract of Physalis Calyx seu Fructus on Avian Infectious Bronchitis Treatment Based on UPLC-Q-TOF-MS and Network Pharmacology [J]. China Animal Husbandry & Veterinary Medicine, 2025, 52(5): 2328-2340.
[3]	LIU Sirui, LIU Hongfei, LIU Dapeng, MU Qiming, TANG Hehe, ZHANG He, ZHANG Yongfu, HOU Shuisheng, ZHOU Zhengkui. Screening of Candidate Genes Regulating Fat Deposition in Pekin Ducks by Integrating Genome and Transcriptome [J]. China Animal Husbandry & Veterinary Medicine, 2025, 52(4): 1468-1477.
[4]	WANG Longxin, YU Simeng, LU Meixi, BAI Xiangxing, HOU Shuisheng. Effects of Different Genotypes of ABCG2 Gene on Eggshell Color, Egg Quality and Laying Performance of Laying Ducks [J]. China Animal Husbandry & Veterinary Medicine, 2025, 52(4): 1671-1680.
[5]	CHENG Yujie, LIU Guowei, LU Enqing, ZHU Min. Protective Effect of Piceatannol on Liver Injury Induced by Deoxynivalenol in Mice [J]. China Animal Husbandry & Veterinary Medicine, 2025, 52(3): 1447-1454.
[6]	LI Yingxiao, YIN Lei, ZHAO Yu, DONG Jianguo, HE Shuhai, QU Zhehui, JIAO Fengchao. Molecular Biological Diagnosis of Co-infection of ALV and MDV in Free Range Local Chickens in Xinyang Area [J]. China Animal Husbandry & Veterinary Medicine, 2025, 52(2): 844-854.
[7]	CHEN Chunhong, SHEN Junye, DAI Chongshan, TANG Shusheng. Research Progress on the Antibacterial Activity of Usnic Acid and Its Development and Utilization [J]. China Animal Husbandry & Veterinary Medicine, 2025, 52(1): 400-410.
[8]	CHI Zhouying, LI Tianxu, WU Yaxin, QU Xiaoyun, LI Sijie, SUN Minhua, ZHANG Jianfeng, LIAO Ming, DU Shouwen. Exploration of Respiratory Tract Response Patterns in Chickens Infected with H9N2 Subtype Avian Influenza Virus [J]. China Animal Husbandry & Veterinary Medicine, 2024, 51(9): 3970-3979.
[9]	LI Xinran, ZHU Lingxin, SONG Huanni, ZHU Xueyan, LI Ruobin, LIU Yang, CAO Changyu. Study on Allicin Alleviating the Liver Injury of Quail Caused by Fumonisin B₁ [J]. China Animal Husbandry & Veterinary Medicine, 2024, 51(9): 4080-4091.
[10]	ZHANG Xiaohan, SUN Lanyuan, SONG Zhuan, HOU Yongqing, WU Tao. Effect of Chebuli Extract on Intestinal and Liver Damage Induced by Lipopolysaccharide in Broilers [J]. China Animal Husbandry & Veterinary Medicine, 2024, 51(8): 3267-3278.
[11]	SU Yuanyuan, YU Chengyuan, ZHANG Mixia, ZHANG Yanjun, ZHUANG Pengwei. Study on the Efficacy of Jianpi Qushi Decoction in the Treatment of Nonalcoholic Fatty Liver in Rats [J]. China Animal Husbandry & Veterinary Medicine, 2024, 51(8): 3662-3675.
[12]	XIAO Jing, WAN Jinlong, YANG Jiangyu, YANG Mengjiao, JIAO Haihong. Pathological and Molecular Biological Diagnosis of Avian Leukosis [J]. China Animal Husbandry & Veterinary Medicine, 2024, 51(6): 2671-2679.
[13]	DONG Yuan, WANG Jianing, LIU Jiaqi, MA Guanghui, ZHU Jie, YU Huan, WANG Huiyan. Effect of Compound Chinese Medicine Preparations on Immune Function of H22 Tumor-bearing Mice [J]. China Animal Husbandry & Veterinary Medicine, 2024, 51(6): 2717-2725.
[14]	SHI Yanyan, CHEN Jianzhong, WU Peifu, WU Yun, CHEN Fenfen. Development Characteristics of Liver Tissue and Expression of Lipoprotein Lipase Gene in Wuliangshan Black-boned Chicken [J]. China Animal Husbandry & Veterinary Medicine, 2024, 51(5): 1988-1997.
[15]	GUO Yu, CHENG Jing, ZUO Yuzhu, FAN Jinghui, JIANG Haijun. Construction and Optimization of Reverse Genetic System of Avian Metapneumovirus Subtype C Expressing Enhanced Green Fluorescent Protein [J]. China Animal Husbandry & Veterinary Medicine, 2024, 51(5): 2091-2100.