Considerable Effects of Caffeinated Coffee on Mouse Liver Function

Document Type : Original paper


1 Proteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

2 Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.

3 Iranian Cancer Control Center (MACSA), Tehran, Iran.

4 Traditional Medicine and Materia Medica Research Center and Department of Tradiiotnal Meicine, School of Traditional Medicine Shahid, Beheshti University of Medical Sciences, Tehran, Iran.

5 Laser Application in Medical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.


Background and objectives: Coffee is a favorable drink in the world with advantages that are documented during different investigations. In the present study, the effect of caffeine which is one of the important compounds of coffee has been evaluated on function of mice liver via network analysis and gene ontology enrichment. Methods: Results of GSE53131 from Gene Expression Omnibus (GEO) were analyzed and the differentially expressed genes (DEGs) were assessed via protein-protein interaction (PPI) network analysis and gene ontology. Cytoscape software and STRING database were used to analyze the data. Results: Effect of caffeine on mice liver was appeared in the gene expression profiles of the mice liver which were fed with caffeinated and decaffeinated coffee. Acat2, Acly, Acss2, Akr1d1, Ehhadh, Elovl2, Fasn, Fdps, Gsta3, Hmgcr, Ldlr, Lss, Mmab, Mvd, Mvk, Nsdhl, Prodh, Rdh11, and Thrsp that are related mostly to lipid metabolism and cholesterol biosynthesis were pointed out as the discriminator genes in response to caffeine  effect on liver function. Conclusion: In conclusion, assessment of mice liver gene expression profiles revealed that lipid metabolism of the mice liver was affected considerably by consumption of caffeinated coffee versus liver of mice that were fed with decaffeinated coffee. Using caffeine as a preventing factor for hepatic disorders is recommended base on the findings of present study.


Main Subjects

  • Nkondjock A. Coffee consumption and the risk of cancer: an overview. Cancer Lett. 2009; 277(2): 121–125.
  • Carlström M, Larsson SC. Coffee consumption and reduced risk of developing type 2 diabetes: a systematic review with meta-analysis. Nutr Rev. 2018; 76(6): 395–417.
  • Ebadi M, Ip S, Bhanji RA, Montano-Loza AJ. Effect of coffee consumption on non-alcoholic fatty liver disease incidence, prevalence and risk of significant liver fibrosis: systematic review with meta-analysis of observational studies. Nutrients. 2021; 13(9): 1–16.
  • Dranoff JA. Coffee consumption and prevention of cirrhosis: in support of the caffeine hypothesis. Gene Exp. 2018; 18(1): 1–3.
  • Kolb H, Kempf K, Martin S. Health effects of coffee: mechanism unraveled? Nutrients. 2020; 12(6): 1–14.
  • Higashi Y. Coffee and endothelial function: a coffee paradox? Nutrients. 2019; 11(9): 1–21.
  • Barnung RB, Nost TH, Ulven SM, Skeie G, Olsen KS. Coffee consumption and whole-blood gene expression in the Norwegian women and cancer post-genome cohort. Nutrients. 2018; 10(8): 1–15.
  • Nakagawa-Senda H, Hachiya T, Shimizu A, Hosono S, Oze I, Watanabe M, Matsuo K, Ito H, Hara M, Nishida Y, Endoh K, Kuriki K, Katsuura-Kamano S, Arisawa K, Nindita Y, Ibusuki R, Suzuki S, Hosono A, Mikami H, Nakamura Y, Takashima N, Nakamura Y, Kuriyama N, Ozaki E, Furusyo N, Ikezaki H, Nakatochi M, Sasakabe T, Kawai S, Okada R, Hishida A, Naito M, Wakai K, Momozawa Y, Kubo M, Tanaka A genome-wide association study in the Japanese population identifies the 12q24 locus for habitual coffee consumption: the J-MICC study. Sci Rep. 2018; 8(1): 1–11.
  • Rezaei Tavirani M, Razzaghi Z, Arjmand B, Vafaee R. Cholesterol metabolism pathway, the main target of coffee. Res J Pharmacogn. 2022; 9(4): 39–47.
  • Vafaee R, Zamanian Azodi M, Rezaei Tavirani M, Razzaghi Z, Arjmand B, Esmaeili S. Cancer chemo-preventive effects of red propolis: a system biology approach. Res J Pharmacogn. 2023; 10(1): 23–29.
  • Katayama M, Donai K, Sakakibara H, Ohtomo Y, Miyagawa M, Kuroda K, Kodama H, Suzuki K, Kasai N, Nishimori K, Uchida T, Watanabe K, Aso H, Isogai E, Sone H, Fukuda T. Coffee consumption delays the hepatitis and suppresses the inflammation related gene expression in the Long-Evans cinnamon rat. Clin Nutr. 2014; 33(2): 302–310.
  • Adan A, Prat G, Fabbri M, Sànchez Turet M. Early effects of caffeinated and decaffeinated coffee on subjective state and gender differences. Prog Neuropsychopharmacol Biol Psychiatry. 2008; 32(7): 1698–1703.
  • Axelson M, Björkhem I, Reihnér E, Einarsson K. The plasma level of 7α-hydroxy-4-cholesten-3-one reflects the activity of hepatic cholesterol 7α-hydroxylase in man. FEBS Lett. 1991; 284(2): 216–218.
  • Petoukhov MV, Weissenhorn W, Svergun DI. Endophilin-A1 BAR domain interaction with arachidonyl CoA. Front Mol Biosci. 2014; 1: 1–8.
  • Van Tamelen E, Willett J, Clayton R, Lord KE. Enzymic conversion of squalene 2, 3-oxide to lanosterol and cholesterol. J Am Chem Soc. 1966; 88(20): 4752–4754.
  • Surdo PL, Bottomley MJ, Calzetta A, Settembre EC, Cirillo A, Pandit S, Ni YG, Hubbard B, Sitlani A, Carfí Mechanistic implications for LDL receptor degradation from the PCSK9/LDLR structure at neutral pH. EMBO Rep. 2011; 12(12): 1300–1305.
  • Yang G, Sun S, He J, Wang Y, Ren T, He H, Gao Enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase (ehhadh) is essential for production of DHA in zebrafish. J Lipid Res. 2023: 64(3): 1–11.
  • Buhaescu I, Izzedine H. Mevalonate pathway: a review of clinical and therapeutical implications. Clin Biochem. 2007; 40(9-10): 575–584.
  • Weerasinghe S, Samantha Dassanayake R. Simulation of structural and functional properties of mevalonate diphosphate decarboxylase (MVD). J Mol Model. 2010; 16(3): 489–498.
  • Tsutsumi H, Moriwaki Y, Terada T, Shimizu K, Shinya K, Katsuyama Y, Ohnishi Structural and molecular basis of the catalytic mechanism of geranyl pyrophosphate C6-methyltransferase: creation of an unprecedented farnesyl pyrophosphate C6-methyltransferase. Angew Chem. 2022; 61(1): 1–9.
  • Bito T, Watanabe F. Biochemistry, function, and deficiency of vitamin B12 in Caenorhabditis elegans. Exp Biol Med. 2016; 241(15): 1663–1668.
  • Goedeke L, Canfrán-Duque A, Rotllan N, Chaube B, Thompson BM, Lee RG, Cline GW, McDonald JG, Shulman GI, Lasunción MA, Suárez Y, Fernández-Hernando MMAB promotes negative feedback control of cholesterol homeostasis. Nat Commun. 2021; 12(1): 1–18.
  • Jensen-Urstad AP, Semenkovich CF. Fatty acid synthase and liver triglyceride metabolism: housekeeper or messenger? Biochim Biophys Acta Mol Cell Biol Lipids. 2012; 1821(5): 747–753.