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Updated: Jul 17, 2025
Author Spotlight: Isolation and Identification of Mesenchymal Stem Cells Derived from Adipose Tissue of Sprague Dawley Rats
Published on: April 7, 2023
Autophagy perturbation upon acute pyrethroid treatment impacts adipogenic commitment of mesenchymal stem cells
Julee Verma1, Ajit Kumar Rai1, Neeraj Kumar Satija1
1Systems Toxicology Group, Food, Drug & Chemical, Environment and Systems Toxicology Division, CSIR-Indian Institute of Toxicology Research, Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow 226001, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
Abstract:
Environmental chemical exposure can cause dysregulation in adipogenesis that can result in metabolic syndrome, which includes insulin resistance, type 2 diabetes, cardiovascular disease, as well as excessive body weight. The role of autophagy in adipocyte differentiation is debatable since both positive and negative effects have been reported. Type-I and type-II synthetic pyrethroids α-cypermethrin (CPM) and permethrin (PER), respectively, are reported to increase adipogenesis in vitro and in vivo. However, it is not known how these pyrethroids affect mesenchymal stem cells (MSCs). Thus, this study focused on evaluating the effect of pyrethroids (CPM and PER) pre-treatment (24 h) on MSC commitment and the regulatory role of autophagy in adipogenic lineage commitment. The formation of adipocytes was observed through nile red staining, perilipin expression by immunoflourescence, and adipogenic markers PPARγ, C/EBPα, and FABP4 by western blotting. It was found that the adipogenic differentiation ability of MSCs was significantly increased upon CPM or PER pre-treatment at 100 μM concentration as evident by lipid accumulation and enhanced expression of adipogenic markers. To assess the involvement of autophagy, the expression of p62 and LC3II were evaluated following pre-treatment. Immunoblotting results revealed an increased expression of p62 and LC3II in CPM or PER pretreated MSCs suggesting CPM and PER mediated inhibition of autophagy at 24 h. Further, an increase was observed in adipogenesis upon CPM or PER pre-treatment in combination with chloroquine, while use of rapamycin during pre-treatment abrogated the effect of CPM and PER. Thus, this study concludes that CPM or PER pre-treatment increases the adipogenic differentiation of MSCs. Since chloroquine also demonstrated similar adipogenic response, it further highlights that 24 h pre-treatment with autophagy modulators to inhibit basal autophagy primes MSCs towards adipogenic lineage.
