Friend or Foe for Obesity: How Hepatokines Remodel Adipose Tissues and Translational Perspective

Overview

Journal Genes Dis

Date 2023 Jul 3

PMID 37396511

Authors

Yao Zhang

Yibing Wang

Junli Liu

Affiliations

Soon will be listed here.

Abstract

Due to excess energy intake and a sedentary lifestyle, the prevalence of obesity is rising steadily and has emerged as a global public health problem. Adipose tissue undergoes structural remodeling and dysfunction in the obese state. Secreted proteins derived from the liver, also termed as hepatokines, exert multiple effects on adipose tissue remodeling and the development of obesity, and has drawn extensive attention for their therapeutic potential in the treatment of obesity and related diseases. Several novel hepatokines and their functions on systemic metabolism have been interrogated recently as well. The drug development programs targeting hepatokines also have shown inspiring benefits in obesity treatment. In this review, we outline how adipose tissue changes during obesity. Then, we summarize and critically analyze the novel findings on the effects of metabolic "beneficial" and metabolic "harmful" hepatokines to adipose tissue. We also discuss the in-depth molecular mechanism that hepatokines may mediate the liver-adipose tissue crosstalk, the novel technologies targeting hepatokines and their receptors to explore their functions, and the potential application of these interventions in clinical practice.

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References

Polyzos S, Kountouras J, Mantzoros C . Obesity and nonalcoholic fatty liver disease: From pathophysiology to therapeutics. Metabolism. 2018; 92:82-97. DOI: 10.1016/j.metabol.2018.11.014. View

Hu W, Chen L . Association of Serum Adropin Concentrations with Diabetic Nephropathy. Mediators Inflamm. 2016; 2016:6038261. PMC: 4980507. DOI: 10.1155/2016/6038261. View

Chen S, Zeng K, Liu Q, Guo Z, Zhang S, Chen X . Adropin deficiency worsens HFD-induced metabolic defects. Cell Death Dis. 2017; 8(8):e3008. PMC: 5596552. DOI: 10.1038/cddis.2017.362. View

Chatterjee P, Seal S, Mukherjee S, Kundu R, Mukherjee S, Ray S . Adipocyte fetuin-A contributes to macrophage migration into adipose tissue and polarization of macrophages. J Biol Chem. 2013; 288(39):28324-30. PMC: 3784748. DOI: 10.1074/jbc.C113.495473. View

Shimamura M, Matsuda M, Kobayashi S, Ando Y, Ono M, Koishi R . Angiopoietin-like protein 3, a hepatic secretory factor, activates lipolysis in adipocytes. Biochem Biophys Res Commun. 2003; 301(2):604-9. DOI: 10.1016/s0006-291x(02)03058-9. View

Banerjee S, Ghoshal S, Stevens J, McCommis K, Gao S, Castro-Sepulveda M . Hepatocyte expression of the micropeptide adropin regulates the liver fasting response and is enhanced by caloric restriction. J Biol Chem. 2020; 295(40):13753-13768. PMC: 7535914. DOI: 10.1074/jbc.RA120.014381. View

Watt M, Miotto P, De Nardo W, Montgomery M . The Liver as an Endocrine Organ-Linking NAFLD and Insulin Resistance. Endocr Rev. 2019; 40(5):1367-1393. DOI: 10.1210/er.2019-00034. View

Morita M, Hashimoto O . Identification and expression of the medaka inhibin βE subunit. Mol Biol Rep. 2019; 46(2):1603-1609. DOI: 10.1007/s11033-019-04607-y. View

Weterman M, Ajubi N, van Dinter I, Degen W, van Muijen G, Ruitter D . nmb, a novel gene, is expressed in low-metastatic human melanoma cell lines and xenografts. Int J Cancer. 1995; 60(1):73-81. DOI: 10.1002/ijc.2910600111. View

10.

Suarez-Zamorano N, Fabbiano S, Chevalier C, Stojanovic O, Colin D, Stevanovic A . Microbiota depletion promotes browning of white adipose tissue and reduces obesity. Nat Med. 2015; 21(12):1497-1501. PMC: 4675088. DOI: 10.1038/nm.3994. View

11.

Peppler W, Castellani L, Root-McCaig J, Townsend L, Sutton C, Frendo-Cumbo S . Regulation of Hepatic Follistatin Expression at Rest and during Exercise in Mice. Med Sci Sports Exerc. 2019; 51(6):1116-1125. DOI: 10.1249/MSS.0000000000001893. View

12.

Lazo M, Zeb I, Nasir K, Tracy R, Budoff M, Ouyang P . Association Between Endogenous Sex Hormones and Liver Fat in a Multiethnic Study of Atherosclerosis. Clin Gastroenterol Hepatol. 2015; 13(9):1686-93.e2. PMC: 4500744. DOI: 10.1016/j.cgh.2014.12.033. View

13.

Caron A, Lee S, Elmquist J, Gautron L . Leptin and brain-adipose crosstalks. Nat Rev Neurosci. 2018; 19(3):153-165. PMC: 5962962. DOI: 10.1038/nrn.2018.7. View

14.

Xu M, Xu H, Lin Y, Sun X, Wang L, Fang Z . LECT2, a Ligand for Tie1, Plays a Crucial Role in Liver Fibrogenesis. Cell. 2019; 178(6):1478-1492.e20. DOI: 10.1016/j.cell.2019.07.021. View

15.

AlQahtani A, OConnor D, Domling A, Goda S . Strategies for the production of long-acting therapeutics and efficient drug delivery for cancer treatment. Biomed Pharmacother. 2019; 113:108750. DOI: 10.1016/j.biopha.2019.108750. View

16.

Georgiadi A, Lopez-Salazar V, Merahbi R, Karikari R, Ma X, Mourao A . Orphan GPR116 mediates the insulin sensitizing effects of the hepatokine FNDC4 in adipose tissue. Nat Commun. 2021; 12(1):2999. PMC: 8137956. DOI: 10.1038/s41467-021-22579-1. View

17.

Berti L, Irmler M, Zdichavsky M, Meile T, Bohm A, Stefan N . Fibroblast growth factor 21 is elevated in metabolically unhealthy obesity and affects lipid deposition, adipogenesis, and adipokine secretion of human abdominal subcutaneous adipocytes. Mol Metab. 2015; 4(7):519-27. PMC: 4481465. DOI: 10.1016/j.molmet.2015.04.002. View

18.

Alapatt P, Guo F, Komanetsky S, Wang S, Cai J, Sargsyan A . Liver retinol transporter and receptor for serum retinol-binding protein (RBP4). J Biol Chem. 2012; 288(2):1250-65. PMC: 3543007. DOI: 10.1074/jbc.M112.369132. View

19.

Shan L, Yu X, Liu Z, Hu Y, Sturgis L, Miranda M . The angiopoietin-like proteins ANGPTL3 and ANGPTL4 inhibit lipoprotein lipase activity through distinct mechanisms. J Biol Chem. 2008; 284(3):1419-24. PMC: 3769808. DOI: 10.1074/jbc.M808477200. View

20.

Scheja L, Heeren J . Metabolic interplay between white, beige, brown adipocytes and the liver. J Hepatol. 2016; 64(5):1176-1186. DOI: 10.1016/j.jhep.2016.01.025. View