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Food Chem Toxicol. 2019 Jun 11;131:110576. doi: 10.1016/j.fct.2019.110576. [Epub ahead of print]

Ivermectin decreases triglyceride accumulation by inhibiting adipogenesis of 3T3-L1 preadipocytes.

Author information

1
Department of Food Science of Massachusetts, Amherst, MA, 01003, United States.
2
Department of Veterinary and Animal Sciences of Massachusetts, Amherst, MA, 01003, United States.
3
Department of Environmental Health Sciences, University of Massachusetts, Amherst, MA, 01003, United States.
4
Department of Food Science of Massachusetts, Amherst, MA, 01003, United States. Electronic address: ypark@foodsci.umass.edu.

Abstract

Ivermectin, a member of the avermectins, is one of the most used anti-parasitic agents, and acts by binding to glutamate-gated chloride channels in invertebrate nerve cells. There is limited information, however, on the effects of ivermectin in non-neural cell, such as adipocytes. The present work aimed to investigate the role of ivermectin in adipogenesis using 3T3-L1 preadipocytes. Ivermectin inhibited the differentiation of preadipocytes and triglyceride (TG) accumulation. In particular, the treatment of ivermectin at the middle to late adipogenic differentiation period (day 2-8) was correlated with the inhibition of fat accumulation. Ivermectin treatment also significantly modulated the mRNA expression of key markers in adipogenesis, fatty acid synthesis, uptake, and oxidation, and enhanced the gene expression of two subunits of the glycine receptor (GlyR). Specifically, the protein levels of peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer-binding protein alpha (C/EBPα), and acetyl-CoA carboxylase (ACC) were reduced. Interestingly, the suppression of TG accumulation by ivermectin was partially abolished by rosiglitazone, a specific PPARγ agonist, but Z-guggulsterone, a selective FXR antagonist, failed to rescue the ivermectin-induced effect on adipogenesis. Lastly, ivermectin prevented adipogenesis induced by permethrin and fipronil. In conclusion, ivermectin inhibits adipogenesis of 3T3-L1 preadipocytes partially via PPARγ & GlyR-dependent, but not FXR-dependent, pathway.

KEYWORDS:

3T3-L1 preadipocyte; Differentiation; GlyR; Ivermectin; PPARγ

PMID:
31199990
DOI:
10.1016/j.fct.2019.110576

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