Skip to main content

Systems biology applied to non-alcoholic fatty liver disease (NAFLD): treatment selection based on the mechanism of action of nutraceuticals


Non-alcoholic fatty liver disease (NAFLD) comprises several liver pathologic states and affects 10%–35% of the population. However, the only known “treatment” for NAFLD is significant weight loss through a lifestyle change, so there is a great need for improvement in the pharmacological management of the disease. As nutraceuticals may alleviate the results of lack of treatment during the first, asymptomatic phase of the disease, we used SIMScells ( and the Therapeutic Performance Mapping System (TPMS), a proprietary systems biology technology of Anaxomics (www.anaxomics. com), to predict the best nutraceuticals to use against NAFLD. We first performed a reprofiling analysis, which led us to identify 33 potential nutraceuticals that could ameliorate the illness. Next, we found the most probable mechanism of action (MoA) of four selected nutraceuticals. Some of these MoAs feature links that have never before been related to the studied pathophysiological mechanisms, thus providing new testable hypotheses. In addition, the MoAs provide two means of treatment selection, according to disease pathophysiological pathways (“motives”) or to each patient’s response to the nutraceuticals (“cluster MoAs”). In conclusion, we use TPMS to predict the molecular mechanistic explanation of the action of the current top nutraceutical used against NAFLD, L-carnitine, highlighting different response subpopulations. We also mechanistically propose the stratification of patients and usefulness of other nutraceuticals (calcitriol and thiamine) on a par or over L-carnitine according to patients’ pathophysiology.

This is a preview of subscription content, access via your institution.


  1. 1.

    Adams LA, Angulo P (2006) Treatment of non-alcoholic fatty liver disease. Postgrad Med J 82(967):315–322

    CAS  Article  Google Scholar 

  2. 2.

    Salt WB 2nd (2004) Nonalcoholic fatty liver disease (NAFLD): a comprehensive review. J Insur Med 36(1):27–41

    Google Scholar 

  3. 3.

    Tiniakos, DG, Vos MB, Brunt EM (2010) Nonalcoholic fatty liver disease: pathology and pathogenesis. Annu Rev Pathol 5:145–171

    CAS  Article  Google Scholar 

  4. 4.

    Kitson MT, Roberts SK (2012) D-livering the message: the importance of vitamin D status in chronic liver disease. J Hepatol 57(4):897–909

    CAS  Article  Google Scholar 

  5. 5.

    Selmi C, Bowlus CL, Keen CL, Gershwin ME (2007) Nonalcoholic fatty liver disease: the new epidemic and the need for novel nutritional approaches. J Med Food 10(4):563–565

    Article  Google Scholar 

  6. 6.

    Promrat K, Kleiner DE, Niemeier HM et al (2010) Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis. Hepatology 51(1):121–129

    CAS  Article  Google Scholar 

  7. 7.

    Masterton GS, Plevris JN, Hayes PC (2010) Review article: omega-3 fatty acids: a promising novel therapy for non-alcoholic fatty liver disease. Aliment Pharmacol Ther 31(7): 679–692

    CAS  Article  Google Scholar 

  8. 8.

    Valls R, Pujol A, Farrés J, Artigas L, Mas JM (2013) Anaxomics’ methodologies: understanding the complexity of biological processes. Barcelona: Anaxomics Biotech

    Google Scholar 

  9. 9.

    Hatzis G, Ziakas P, Kavantzas N, et al (2013) Melatonin attenuates high fat diet-induced fatty liver disease in rats. World J Hepatol 5(4):160–169

    Google Scholar 

  10. 10.

    Geier A (2011) Shedding new light on vitamin D and fatty liver disease. J Hepatol 55(2):273–275

    Article  Google Scholar 

  11. 11.

    Kang JS, Lee WK, Yoon WK et al (2011) A combination of grape extract, green tea extract and L-carnitine improves high-fat diet-induced obesity, hyperlipidemia and non-alcoholic fatty liver disease in mice. Phytother Res 25(12):1789–1795

    CAS  Article  Google Scholar 

  12. 12.

    Lim, CY, Jun DW, Jang SS, Cho WK, Chae JD, Jun JH (2010) Effects of carnitine on peripheral blood mitochondrial DNA copy number and liver function in non-alcoholic fatty liver disease. Korean J Gastroenterol 55(6):384–389

    Article  Google Scholar 

  13. 13.

    Xia, Y, Li Q, Zhong W, Dong J, Wang Z, Wang C (2011) Lcarnitine ameliorated fatty liver in high-calorie diet/STZinduced type 2 diabetic mice by improving mitochondrial function. Diabetol Metab Syndr 3:31

    CAS  Article  Google Scholar 

  14. 14.

    Jun, DW, Cho WK, Jun JH (2011) Prevention of free fatty acid-induced hepatic lipotoxicity by carnitine via reversal of mitochondrial dysfunction. Liver Int 31(9):1315–1324

    CAS  Article  Google Scholar 

Download references

Author information



Corresponding author

Correspondence to Teresa Sardón.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Perera, S., Artigas, L., Mulet, R. et al. Systems biology applied to non-alcoholic fatty liver disease (NAFLD): treatment selection based on the mechanism of action of nutraceuticals. Nutrafoods 13, 61–68 (2014).

Download citation


  • mechanism of action
  • nutraceuticals
  • patient stratification
  • systems biology
  • TPMS