Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter November 7, 2016

Metabolite profiling can change health-care delivery to obese patients with fatty liver disease: the search for biomarkers

  • Jordi Camps EMAIL logo and Jorge Joven

Abstract

Comorbidities associated with obesity have become a worldwide public health concern. Obesity-associated hepatic steatosis is not benign, and the risk of developing severe liver disease is high. Currently, biopsy is the only clinical tool available for the diagnosis of pathological alterations in the liver. However, the procedure is painful and not without risk. As such, there is a need to identify non-invasive biomarkers of steatosis. There has been considerable progress in this area, but research appears to be limited to measurements of levels of certain parameters in patients with liver impairment relative to those of healthy controls. The clinically relevant aim should be to distinguish, at an early stage, those obese individuals with liver steatosis from those obese individuals without it. Plasma constituents that act as surrogates of altered hepatic energy metabolism in response to food intake are likely candidates. Targeted metabolomics, combined with quantitation of the metabolites involved, has been shown to be an efficient measurement tool. Indeed, the evaluation of exhaled volatile compounds might be sufficient, while other rapid, sensitive, and reproducible methods have been validated in preliminary studies in various clinical settings. Metabolomics methods are promising but require considerable expertise and sophisticated (and expensive) equipment not readily available in all centers. The challenge is to adapt this newly acquired, expanding knowledge to current, reasonably equipped clinical laboratories, while substantially reducing costs. Good outcomes are urgently required if effective prevention programs are to be developed to decrease the prevalence of liver disease.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

1. Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of obesity among adults: United States, 2011–2012. NCHS Data Brief 2013;131:1–8.Search in Google Scholar

2. Joven J, Micol V, Segura-Carretero A, Alonso-Villaverde C, Menendez JA. Polyphenols and the modulation of gene expression pathways: can we eat our way out of the danger of chronic disease? Crit Rev Food Sci Nutr 2013;54:985–1001.10.1080/10408398.2011.621772Search in Google Scholar PubMed

3. Hagström H, Stål P, Hultcrantz R, Hemmingsson T, Andreasson A. Overweight in late adolescence predicts development of severe liver disease later in life: A 39years follow-up study. J Hepatol 2016;65:363–8.10.1016/j.jhep.2016.03.019Search in Google Scholar PubMed

4. Guy CD, Suzuki A, Burchette JL, Brunt EM, Abdelmalek MF, Cardona D, et al. Nonalcoholic steatohepatitis clinical research network. Co-staining for keratins 8/18 plus ubiquitin improves detection of hepatocyte injury in nonalcoholic fatty liver disease. Hum Pathol 2012;43:790–800.10.1016/j.humpath.2011.07.007Search in Google Scholar PubMed PubMed Central

5. Serviddio G, Bellanti F, Vendemiale G. Free radical biology for medicine: learning from nonalcoholic fatty liver disease. Free Radic Biol Med 2013;65:952–68.10.1016/j.freeradbiomed.2013.08.174Search in Google Scholar PubMed

6. Roessner U, Bowne J. What is metabolomics all about? Biotechniques 2009;46:363–5.10.2144/000113133Search in Google Scholar PubMed

7. Rauschert S, Uhl O, Koletzko B, Hellmuth C. Metabolomic biomarkers for obesity in humans: a short review. Ann Nutr Metab 2014;64:314–24.10.1159/000365040Search in Google Scholar PubMed

8. Mirza MS. Obesity, visceral fat and NAFLD: querying the role of adipokines in the progression of nonalcoholic fatty liver disease. ISRN Gastroenterol 2011;2011:592404.10.5402/2011/592404Search in Google Scholar PubMed PubMed Central

9. Rogge MM. The role of impaired mitochondrial lipid oxidation in obesity. Biol Res Nurs 2009;10:356–73.10.1177/1099800408329408Search in Google Scholar PubMed

10. de Ferranti S, Mozaffarian D. The perfect storm: obesity, adipocyte dysfunction, and metabolic consequences. Clin Chem 2008;54:945–55.10.1373/clinchem.2007.100156Search in Google Scholar PubMed

11. Ron D, Walter P. Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol 2007;8:519–29.10.1038/nrm2199Search in Google Scholar PubMed

12. Camps J, García-Heredia A, Hernández-Aguilera A, Joven J. Paraoxonases, mitochondrial dysfunction and non-communicable diseases. Chem Biol Interact 2016; doi: 10.1016/j.cbi.2016.04.005. [Epub ahead of print].Search in Google Scholar PubMed

13. Camps J, Rodríguez-Gallego E, García-Heredia A, Triguero I, Riera-Borrull M, Hernández-Aguilera A, et al. Paraoxonases and chemokine (C-C motif) ligand-2 in non-communicable diseases. Adv Clin Chem 2014;63:247–308.10.1016/B978-0-12-800094-6.00007-8Search in Google Scholar PubMed

14. Hernández-Aguilera A, Rull A, Rodríguez-Gallego E, Riera-Borrull M, Luciano-Mateo F, Camps J, et al. Mitochondrial dysfunction: a basic mechanism in inflammation-related non-communicable diseases and therapeutic opportunities. Mediators Inflamm 2013;2013:135698.10.1155/2013/135698Search in Google Scholar PubMed PubMed Central

15. Hernández-Aguilera A, Fernández-Arroyo S, Luciano-Mateo F, Cabré N, Camps J, López-Miranda J, et al. Chronic nutrient toxicity causing metabolic variations and high risk of disease through changes in DNA-methylation. Food Chem Toxicol 2016;96:191–204.10.1016/j.fct.2016.08.006Search in Google Scholar PubMed

16. Haas R, Smith J, Rocher-Ros V, Nadkarni S, Montero-Melendez T, D’Acquisto F, et al. Lactate regulates metabolic and pro-inflammatory circuits in control of T cell migration and effector functions. PLoS Biol 2015;13:e1002202.10.1371/journal.pbio.1002202Search in Google Scholar PubMed PubMed Central

17. Liu C, Wu J, Zhu J, Kuei C, Yu J, Shelton J, et al. Lactate inhibits lipolysis in fat cells through activation of an orphan G-protein-coupled receptor, GPR81. J Biol Chem 2009;284:2811–2.10.1074/jbc.M806409200Search in Google Scholar PubMed

18. Hashimoto T, Hussien R, Brooks GA. Co-localization of MCT1, CD147, and LDH in mitochondrial inner membrane of L6 muscle cells: evidence of a mitochondrial lactate oxidation complex. Am J Physiol Endocrinol Metab 2006;290:E1237–44.10.1152/ajpendo.00594.2005Search in Google Scholar PubMed

19. Gonzalez NS, Communi D, Hannedouche S, Boeynaems JM. The fate of P2Y- related orphan receptors: GPR80/99 and GPR91 are receptors of dicarboxylic acids. Purinergic Signal 2004;1:17–20.10.1007/s11302-004-5071-6Search in Google Scholar PubMed PubMed Central

20. Shimazu T, Hirschey MD, Newman J, He W, Shirakawa K, Le Moan N, et al. Suppression of oxidative stress by β-hydroxybutyrate, an endogenous histone deacetylase inhibitor. Science 2013;339:211–4.10.1126/science.1227166Search in Google Scholar PubMed PubMed Central

21. Haas R, Cucchi D, Smith J, Pucino V, Macdougall CE, Mauro C. Intermediates of metabolism: from bystanders to signalling molecules. Trends Biochem Sci 2016; 41:460–71.10.1016/j.tibs.2016.02.003Search in Google Scholar PubMed

22. Alkhouri N, Cikach F, Eng K, Moses J, Patel N, Yan C, et al. Analysis of breath volatile organic compounds as non-invasive tool to diagnose non-alcoholic fatty liver disease in children. Eur J Gastroenterol Hepatol 2014;26:82–7.10.1097/MEG.0b013e3283650669Search in Google Scholar PubMed

23. Hanouneh IA, Zein NN, Cikach F, Dababneh D, Grove D, Alkhouri N, et al. The breathprints in patients with liver disease identify novel breath biomarkers of alcoholic hepatitis. Clin Gastroenterol Hepatol 2014;12:516–23.10.1016/j.cgh.2013.08.048Search in Google Scholar PubMed PubMed Central

24. Alkhouri N, Eng K, Cikach F, Patel N, Yan C, Brindle A, et al. Breathprints of childhood obesity: changes in volatile organic compounds in obese children compared with lean controls. Pediatr Obes 2015;10:23–9.10.1111/j.2047-6310.2014.221.xSearch in Google Scholar PubMed PubMed Central

25. Smith D, Španěl P, Herbig J, Beauchamp J. Mass spectrometry for real-time quantitative breath analysis. J Breath Res 2014;8:027101.10.1088/1752-7155/8/2/027101Search in Google Scholar PubMed

26. Rodríguez-Gallego E, Guirro M, Riera-Borrull M, Hernández-Aguilera A, Mariné-Casadó R, Fernández-Arroyo S, et al. Mapping of the circulating metabolome reveals α-ketoglutarate as a predictor of morbid obesity-associated non-alcoholic fatty liver disease. Int J Obes (Lond) 2015;39:279–87.10.1038/ijo.2014.53Search in Google Scholar PubMed

27. Riera-Borrull M, Rodríguez-Gallego E, Hernández-Aguilera A, Luciano F, Ras R, Cuyàs E, et al. Exploring the process of energy generation in pathophysiology by targeted metabolomics: performance of a simple and quantitative Method. J Am Soc Mass Spectrom 2016;27:168–77.10.1007/s13361-015-1262-3Search in Google Scholar PubMed

28. Bao XR, Ong SE, Goldberger O, Peng J, Sharma R, Thompson DA, et al. Mitochondrial dysfunction remodels one-carbon metabolism in human cells. Elife 2016;5:e10575.10.7554/eLife.10575Search in Google Scholar PubMed PubMed Central

29. Ron-Harel N, Santos D, Ghergurovich JM, Sage PT, Reddy A, Lovitch SB, et al. Mitochondrial biogenesis and proteome remodeling promote one-carbon metabolism for T cell activation. Cell Metab 2016;24:104–117.10.1016/j.cmet.2016.06.007Search in Google Scholar PubMed PubMed Central

30. Long JZ, Svensson KJ, Bateman LA, Lin H, Kamenecka T, Lokurkar IA, et al. The secreted enzyme PM20D1 regulates lipidated amino acid uncouplers of mitochondria. Cell 2016;166:424–35.10.1016/j.cell.2016.05.071Search in Google Scholar PubMed PubMed Central

31. Guerrero S, Martínez-García G, Serafín V, Agüí L, Yáñez-Sedeño P, Pingarrón JM. Electrochemical immunosensor for sensitive determination of the anorexigen peptide YY at grafted reduced graphene oxide electrode platforms. Analyst 2015;140:7527–33.10.1039/C5AN01185JSearch in Google Scholar

Received: 2016-8-29
Accepted: 2016-10-1
Published Online: 2016-11-7
Published in Print: 2017-3-1

©2017 Walter de Gruyter GmbH, Berlin/Boston

Downloaded on 28.3.2024 from https://www.degruyter.com/document/doi/10.1515/cclm-2016-0762/pdf
Scroll to top button