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



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.


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.


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.


Niclosamide piperazine salt may hold the promise to become an alternative to NEN as a drug lead for the treatment of obesity and T2D.

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High-fat diet


Niclosamide ethanolamine salt


Niclosamide piperazine salt


Type 2 diabetes


Tetramethylrhodamine ethyl ester


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Correspondence to Shengkan Jin.

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This study was funded by Mito BioPharm.

Conflict of interest

S.J. is a founder of Mito BioPharm, which has licensed the patents surrounding the development of chemical mitochondrial uncouplers, including niclosamide ethanolamine and niclosamide piperazine (described here), for treating metabolic diseases.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Guo, J., Tao, H., Alasadi, A. et al. Niclosamide piperazine prevents high-fat diet-induced obesity and diabetic symptoms in mice. Eat Weight Disord 24, 91–96 (2019).

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  • Diabetes
  • Mitochondrial uncoupler
  • Niclosamide
  • Obesity