Asprosin Contributes to Nonalcoholic Fatty Liver Disease Through Regulating Lipid Accumulation and Inflammatory Response Via AMPK Signaling

Overview

Journal Immun Inflamm Dis

Specialties Allergy & Immunology
Infectious Diseases

Date 2023 Aug 30

PMID 37647445

Authors

Bo Zhang

Jinger Lu

Yuhua Jiang

Yan Feng

Affiliations

Soon will be listed here.

Abstract

Background: Nonalcoholic fatty liver disease (NAFLD) is a primary contributor to liver-related morbidity and mortality. Asprosin has been reported to be implicated in NAFLD.

Aims: This work is to illuminate the effects of Asprosin on NAFLD and the possible downstream mechanism.

Materials & Methods: The weight of NAFLD mice induced by a high-fat diet was detected. Quantitative reverse-transcription polymerase chain reaction (RT-qPCR) examined serum Asprosin expression. RT-qPCR and western blot analysis examined Asprosin expression in mice liver tissues. Intraperitoneal glucose tolerance test (IPGTT) and intraperitoneal insulin tolerance test (IPITT) were implemented. Biochemical kits tested liver enzyme levels in mice serum and liver tissues. Hematoxylin and eosin staining evaluated liver histology. Liver weight was also tested and oil red O staining estimated lipid accumulation. RT-qPCR and western blot analysis analyzed the expression of gluconeogenesis-, fatty acid biosynthesis-, fatty acid oxidation-, and inflammation-associated factors. Besides, western blot analysis examined the expression of AMP-activated protein kinase (AMPK)/p38 signaling-associated factors. In palmitic acid (PA)-treated mice hepatocytes, RT-qPCR and western blot analysis examined Asprosin expression. Lipid accumulation, gluconeogenesis, fatty acid biosynthesis, fatty acid oxidation, and inflammation were appraised again.

Results: Asprosin was overexpressed in the serum and liver tissues of NAFLD mice and PA-treated mice hepatocytes. Asprosin interference reduced mice body and liver weight, improved glucose tolerance and diminished liver injury in vivo. Asprosin knockdown alleviated lipid accumulation and inflammatory infiltration both in vitro and in vivo. Additionally, Asprosin absence activated AMPK/p38 signaling and AMPK inhibitor Compound C reversed the impacts of Asprosin on lipid accumulation and inflammatory response.

Conclusion: Collectively, Asprosin inhibition suppressed lipid accumulation and inflammation to obstruct NAFLD through AMPK/p38 signaling.

Citing Articles

Association between neutrophil-to-high-density lipoprotein cholesterol ratio and metabolic dysfunction-associated steatotic liver disease and liver fibrosis in the US population: a nationally representative cross-sectional study using NHANES data....

Lu Y, Xu X, Wu J, Ji L, Huang H, Chen M BMC Gastroenterol. 2024; 24(1):300.

PMID: 39237899 PMC: 11378436. DOI: 10.1186/s12876-024-03394-6.

Asprosin: its function as a novel endocrine factor in metabolic-related diseases.

Zhang Y, Yang P, Zhang X, Liu S, Lou K J Endocrinol Invest. 2024; 47(8):1839-1850.

PMID: 38568373 DOI: 10.1007/s40618-024-02360-z.

MCC950 Ameliorates Diabetic Muscle Atrophy in Mice by Inhibition of Pyroptosis and Its Synergistic Effect with Aerobic Exercise.

Yan X, Fu P, Zhang Y, Ling D, Reynolds L, Hua W Molecules. 2024; 29(3).

PMID: 38338456 PMC: 10856337. DOI: 10.3390/molecules29030712.

Asprosin contributes to nonalcoholic fatty liver disease through regulating lipid accumulation and inflammatory response via AMPK signaling.

Zhang B, Lu J, Jiang Y, Feng Y Immun Inflamm Dis. 2023; 11(8):e947.

PMID: 37647445 PMC: 10436697. DOI: 10.1002/iid3.947.

References

Arrese M, Cabrera D, Kalergis A, Feldstein A . Innate Immunity and Inflammation in NAFLD/NASH. Dig Dis Sci. 2016; 61(5):1294-303. PMC: 4948286. DOI: 10.1007/s10620-016-4049-x. View

Andersen C . Lipid Metabolism in Inflammation and Immune Function. Nutrients. 2022; 14(7). PMC: 9002396. DOI: 10.3390/nu14071414. View

Juanola O, Martinez-Lopez S, Frances R, Gomez-Hurtado I . Non-Alcoholic Fatty Liver Disease: Metabolic, Genetic, Epigenetic and Environmental Risk Factors. Int J Environ Res Public Health. 2021; 18(10). PMC: 8155932. DOI: 10.3390/ijerph18105227. View

Chi C, Teliewubai J, Lu Y, Fan X, Yu S, Xiong J . Comparison of various lipid parameters in association of target organ damage: a cohort study. Lipids Health Dis. 2018; 17(1):199. PMC: 6109323. DOI: 10.1186/s12944-018-0800-y. View

Yuan M, Li W, Zhu Y, Yu B, Wu J . Asprosin: A Novel Player in Metabolic Diseases. Front Endocrinol (Lausanne). 2020; 11:64. PMC: 7045041. DOI: 10.3389/fendo.2020.00064. View

Lee T, Yun S, Jeong J, Jung T . Asprosin impairs insulin secretion in response to glucose and viability through TLR4/JNK-mediated inflammation. Mol Cell Endocrinol. 2019; 486:96-104. DOI: 10.1016/j.mce.2019.03.001. View

Qu W, Ma T, Cai J, Zhang X, Zhang P, She Z . Liver Fibrosis and MAFLD: From Molecular Aspects to Novel Pharmacological Strategies. Front Med (Lausanne). 2021; 8:761538. PMC: 8568774. DOI: 10.3389/fmed.2021.761538. View

Tilg H, Adolph T, Dudek M, Knolle P . Non-alcoholic fatty liver disease: the interplay between metabolism, microbes and immunity. Nat Metab. 2021; 3(12):1596-1607. DOI: 10.1038/s42255-021-00501-9. View

Saikia R, Joseph J . AMPK: a key regulator of energy stress and calcium-induced autophagy. J Mol Med (Berl). 2021; 99(11):1539-1551. DOI: 10.1007/s00109-021-02125-8. View

10.

Sen P, Qadri S, Luukkonen P, Ragnarsdottir O, McGlinchey A, Jantti S . Exposure to environmental contaminants is associated with altered hepatic lipid metabolism in non-alcoholic fatty liver disease. J Hepatol. 2021; 76(2):283-293. DOI: 10.1016/j.jhep.2021.09.039. View

11.

Noor H, Mou N, Salem L, Shimul M, Biswas S, Akther R . Anti-inflammatory Property of AMP-activated Protein Kinase. Antiinflamm Antiallergy Agents Med Chem. 2019; 19(1):2-41. PMC: 7460777. DOI: 10.2174/1871523018666190830100022. View

12.

Duan Y, Pan X, Luo J, Xiao X, Li J, Bestman P . Association of Inflammatory Cytokines With Non-Alcoholic Fatty Liver Disease. Front Immunol. 2022; 13:880298. PMC: 9122097. DOI: 10.3389/fimmu.2022.880298. View

13.

Miao Y, Qin H, Zhong Y, Huang K, Rao C . Novel adipokine asprosin modulates browning and adipogenesis in white adipose tissue. J Endocrinol. 2021; 249(2):83-93. PMC: 8052515. DOI: 10.1530/JOE-20-0503. View

14.

Ahmad A, Makhmutova Z, Cao W, Majaz S, Amin A, Xie Y . Androgen receptor, a possible anti-infective therapy target and a potent immune respondent in SARS-CoV-2 spike binding: a computational approach. Expert Rev Anti Infect Ther. 2023; 21(3):317-327. DOI: 10.1080/14787210.2023.2179035. View

15.

Blaszczak A, Jalilvand A, Hsueh W . Adipocytes, Innate Immunity and Obesity: A Mini-Review. Front Immunol. 2021; 12:650768. PMC: 8264354. DOI: 10.3389/fimmu.2021.650768. View

16.

Zhang B, Lu J, Jiang Y, Feng Y . Asprosin contributes to nonalcoholic fatty liver disease through regulating lipid accumulation and inflammatory response via AMPK signaling. Immun Inflamm Dis. 2023; 11(8):e947. PMC: 10436697. DOI: 10.1002/iid3.947. View

17.

Peiseler M, Schwabe R, Hampe J, Kubes P, Heikenwalder M, Tacke F . Immune mechanisms linking metabolic injury to inflammation and fibrosis in fatty liver disease - novel insights into cellular communication circuits. J Hepatol. 2022; 77(4):1136-1160. DOI: 10.1016/j.jhep.2022.06.012. View

18.

Xu N, Luo H, Li M, Wu J, Wu X, Chen L . β-patchoulene improves lipid metabolism to alleviate non-alcoholic fatty liver disease via activating AMPK signaling pathway. Biomed Pharmacother. 2020; 134:111104. DOI: 10.1016/j.biopha.2020.111104. View

19.

Greenhill C . Liver: Asprosin - new hormone involved in hepatic glucose release. Nat Rev Endocrinol. 2016; 12(6):312. DOI: 10.1038/nrendo.2016.66. View

20.

Shabir K, Brown J, Afzal I, Gharanei S, Weickert M, Barber T . Asprosin, a novel pleiotropic adipokine implicated in fasting and obesity-related cardio-metabolic disease: Comprehensive review of preclinical and clinical evidence. Cytokine Growth Factor Rev. 2021; 60:120-132. DOI: 10.1016/j.cytogfr.2021.05.002. View