Niclosamide as an anti-obesity drug: an experimental study

  • Ali I. Al-Gareeb
  • Khalid D. Aljubory
  • Hayder M. Alkuraishy
Original Article

Abstract

Background

Niclosamide is a well-known anthelminthic drug that exert its effects at least in part through induction of mitochondrial uncoupling. The cycling of mitochondrial proton plays an essential role in regulation of basal metabolic rate, so modulation of mitochondrial uncoupling may be helpful approach to fight obesity.

Objective

To assess the anti-obesity effects of niclosamide on mice with induced obesity.

Materials and methods

Thirty male Albino mice, 8–10 weeks old, were divided randomly and equally in to three groups; Group 1 fed with standard diet, whereas both Groups 2 and 3 were fed with high fat diet (HFD). At 10 weeks, the studied groups continue in the same type of diet as before for another 4 weeks, but additionally both of Group1 and 2 received placebo treatment as normal control and high fat diet control respectively, whereas Group 3 received oral niclosamide (140 mg/kg/day) as treatment group. The anti-obesity effects of niclosamide were evaluated by testing its effects on food intake, bodyweight, glycemic indices, and lipid profile.

Result

It was found that administration of niclosamide 140 mg/kg/day to HFD fed mice (Group3) for 4 weeks resulted in significant (P < 0.05) decline in the food intake and bodyweight of this group as compared with HFD control. Furthermore, niclosamide also resulted in significant (P < 0.05) lowering of the fasting blood glucose, fasting plasma insulin and improve insulin resistance. Likewise, niclosamide ameliorates the harmful effects of HFD on lipid profile by significant lowering of cholesterol, triglycerides, and LDL (P < 0.05).

Conclusion

Niclosamide has promising effects as an anti-obesity drug. It not just lowers bodyweight in mice, but, at the same time, it reverses metabolic disturbance induced by obesity.

Keywords

Niclosamide Obesity Mitochondrial uncoupling Lipid profile 

References

  1. 1.
    Suastika K (2006) Update in the management of obesity. Acta Med Indones 38(4):231–237PubMedGoogle Scholar
  2. 2.
    Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C et al (2013) Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 30;384(9945):766–781. doi:10.1016/S0140-6736(14)60460-8.CrossRefGoogle Scholar
  3. 3.
    Fisher K, Hardie TL, Ranjan S, Peterson J (2016) Utilizing health records to characterize obesity, comorbidities, and health-care services in one human service agency in the US. J Intell Disabil 1, 1744629516660417. doi:10.1177/1744629516660417 Google Scholar
  4. 4.
    Pi­Sunyer X (2009) The medical risks of obesity. Postgrad Med 121(6):21–33. doi:10.3810/pgm.2009.11.2074 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Kyle TK, Dhurandhar EJ, Allison DB (2016) Regarding obesity as a disease: evolving policies and their implications. Endocrinol Metab Clin N Am 45(3):511–520. doi:10.1016/j.ecl.2016.04.004 CrossRefGoogle Scholar
  6. 6.
    Lin CK, Bai MY, Hu TM, Wang YC, Chao TK, Weng SJ et al (2016) Preclinical evaluation of a nanoformulated antihelminthic, niclosamide, in ovarian cancer. Oncotarget 7(8):8993–9006. doi:10.18632/oncotarget.7113 CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Nassir F, Ibdah JA (2014) Role of mitochondria in nonalcoholic fatty liver disease. Int J Mol Sci 15(5):8713­8742. doi:10.3390/ijms15058713 CrossRefPubMedCentralGoogle Scholar
  8. 8.
    Tao H, Zhang Y, Zeng X, Shulman GI, Jin S (2014) Niclosamide ethanolamine-induced mild mitochondrial uncoupling improves diabetic symptoms in mice. Nat Med 20(11):1263–1269. doi:10.1038/nm.3699 CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Geloneze B, Tambascia MA (2006) Laboratorial evaluation and diagnosis of insulin resistance. Arq Bras Endocrinol Metabol 50(2):208­215.Google Scholar
  10. 10.
    Rifai N, Warnick GR (2006) Measurement of lipids, lipoproteins, and apolipoproteins. In: Burtis CA, Ashwood ER, Bruns DE (eds) Tietz textbook of clinical chemistry and molecular diagnosis. 4th ed. Elsevier Saunders, St. Louis, pp 938–952Google Scholar
  11. 11.
    Mykkänen OT, Huotari A, Herzig KH, Dunlop TW, Mykkänen H, Kirjavainen PV (2014) Wild blueberries (Vaccinium myrtillus) alleviate inflammation and hypertension associated with developing obesity in mice fed with a high-fat diet. PLoS One 9(12):e114790. doi:10.1371/journal.pone.0114790 CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Fan Y, Liu Y, Xue K, Gu G, Fan W, Xu Y, Ding Z (2015) Diet-induced obesity in male C57BL/6 mice decreases fertility as a consequence of disrupted blood-testis barrier. PLoS One 10(4):e0120775. doi:10.1371/journal.pone.0120775 CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Bahceci M, Tuzcu A, Akkus M, Yaldiz M, Ozbay A (1999) The effect of high-fat diet on the development of obesity and serum leptin level in rats. Eat Weight Disord 4(3):128–132CrossRefPubMedGoogle Scholar
  14. 14.
    Anderson LM, Reilly EE, Schaumberg K, Dmochowski S, Anderson DA (2016) Contributions of mindful eating, intuitive eating, and restraint to BMI, disordered eating, and meal consumption in college students. Eat Weight Disord 21:83. doi:10.1007/s40519-015-0210-3 CrossRefPubMedGoogle Scholar
  15. 15.
    Li Y, Li PK, Roberts MJ, Arend RC, Samant RS, Buchsbaum DJ (2014) Multi-targeted therapy of cancer by niclosamide: a new application for an old drug. Cancer Lett 349(1):8–14. doi:10.1016/j.canlet.2014.04.003 CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Vernochet C, Mourier A, Bezy O, Macotela Y, Boucher J, Rardin MJ et al (2012) Adipose-specific deletion of TFAM increases mitochondrial oxidation and protects mice against obesity and insulin resistance. Cell Metab 16(6):765–776. doi:10.1016/j.cmet.2012.10.016 CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Turchiano M, Sweat V, Fierman A, Convit A (2012) Obesity, metabolic syndrome, and insulin resistance in Minority Urban High School Students. Arch Pediatr Adolesc Med 166(11):1030–1036. doi:10.1001/archpediatrics.2012.1263 CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Choi JH, Pichiah PB, Kim MJ, Cha YS (2016) Cheonggukjang, a soybean paste fermented with B. licheniformis-67 prevents weight gain and improves glycemic control in high fat diet induced obese mice. J Clin Biochem Nutr 59(1):31–38. doi:10.3164/jcbn.15-30 CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Jung MJ, Lee J, Shin NR, Kim MS, Hyun DW, Yun JH et al (2016) Chronic repression of mTOR complex 2 induces changes in the Gut microbiota of diet-induced obese mice. Sci Rep 29;6:30887. doi:10.1038/srep30887 CrossRefGoogle Scholar
  20. 20.
    Kawano Y, Cohen DE (2013) Mechanisms of hepatic triglyceride accumulation in non-alcoholic fatty liver disease. J Gastroenterol 48(4):434–441. doi:10.1007/s00535-013-0758-5 CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Moran-Ramos S, Tovar AR, Torres N (2012) Diet: friend or foe of enteroendocrine cells—how it interacts with enteroendocrine cells. Adv Nutr 3(1):8–20. doi:10.3945/an.111.000976 CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Grahame Hardie D (2011) AMP-activated protein kinase—an energy sensor that regulates all aspects of cell function. Genes Dev 25(18):1895–1908. doi:10.1101/gad.17420111 CrossRefPubMedGoogle Scholar
  23. 23.
    Chun-Ching Shih, Jin-Bin Wu, Jia-Ying Jian, Cheng-Hsiu Lin, Hui-Ya Ho (2015) (–)-Epicatechin-3-O-β-d-allopyranoside from Davallia formosana, prevents diabetes and hyperlipidemia by regulation of glucose transporter 4 and AMP-activated protein kinase phosphorylation in high-fat-fed mice. Int J Mol Sci 16(10):24983–25001. doi:10.3390/ijms161024983 CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    C Podrini, EL Cambridge, CJ Lelliott, Damian M et al (2013) High-fat feeding rapidly induces obesity and lipid derangements in C57BL/6 N mice. Mamm Genome 24(5–6):240–251. doi:10.1007/s00335-013-9456-0 CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Shaodong Guo (2014) Insulin signaling, resistance, and the metabolic syndrome: insights from mouse models to disease mechanisms. J Endocrinol 220(2):T1–T23. doi:10.1530/JOE-13-0327 CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    SA Mostafa, MJ Davies, DH Morris et al (2012) The association of the triglyceride-to-HDL cholesterol ratio with insulin resistance in white european and south asian men and women. PLoS One 7(12):e50931. doi:10.1371/journal.pone.0050931 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2017

Authors and Affiliations

  1. 1.Clinical Pharmacology and Therapeutics, Department of Clinical Pharmacology and Therapeutics, College of MedicineAl-Mustansiriya UniversityBaghdadIraq
  2. 2.Clinical Pharmacist at Ministry of HealthBaghdadIraq
  3. 3.Clinical Pharmacology and Therapeutics, College of MedicineAl-Mustansiriya UniversityBaghdadIraq

Personalised recommendations