Niclosamide piperazine prevents high-fat diet-induced obesity and diabetic symptoms in mice

Jingjing Guo, Hanlin Tao, Amer Alasadi, Qingrong Huang, Shengkan Jin

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Purpose: Obesity and type 2 diabetes (T2D) have become the major public health challenges globally. Mitochondrial uncoupling, which reduces intracellular lipid loads and corrects the underlying cause of insulin resistance, has emerged as a promising anti-obese and anti-diabetic intervention. Niclosamide is an anthelmintic drug approved by the US FDA with the mechanism of action that uncouples mitochondria of parasitic worms. Recently, niclosamide ethanolamine salt (NEN) was found to be a safe and effective hepatic mitochondrial uncoupler for the prevention and treatment of obesity and T2D in mouse models. The striking features of NEN prompt us to examine the anti-obese and anti-diabetic efficacy of other salt forms of niclosamide, with the ultimate goal to identify a suitable salt formulation for future clinical development. Here, we report the study with niclosamide piperazine salt (NPP), another salt form of niclosamide with documented safety profile. Methods: Mitochondrial uncoupling activity of NEN and NPP were determined by oxygen consumption assay with Seahorse XF24e Analyzer, as well as by mitochondrial membrane potential measurement in cultured cells. The in vivo anti-diabetic and anti-obesity activities were determined in C57BL/6J mice fed high-fat diet (HFD) or HFD containing 2000 ppm. NPP for 11 weeks. Results: Niclosamide piperazine salt showed a comparable mitochondrial uncoupling activity to NEN. Oral administration of NPP significantly reduced HFD-induced obesity, hyperglycemia and hepatic steatosis, and sensitized the insulin responses in mice. Conclusions: Niclosamide piperazine salt may hold the promise to become an alternative to NEN as a drug lead for the treatment of obesity and T2D. No level of evidence Animal study.

Original languageEnglish (US)
Pages (from-to)91-96
Number of pages6
JournalEating and Weight Disorders
Volume24
Issue number1
DOIs
StatePublished - Feb 13 2019

All Science Journal Classification (ASJC) codes

  • Clinical Psychology
  • Psychiatry and Mental health

Keywords

  • Diabetes
  • Mitochondrial uncoupler
  • Niclosamide
  • Obesity

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