<bold> <roman>β</roman> </bold>-Cypermethrin promotes the adipogenesis of 3T3-L1 cells via inducing autophagy and shaping an adipogenesis-friendly microenvironment

Abstract

<jats:title>Abstract</jats:title> <jats:p>The toxicity of synthetic pyrethroids has garnered attention, and studies have revealed that pyrethroids promote fat accumulation and lead to obesity in mice. Nevertheless, the effect of β-cypermethrin (β-CYP) on adipogenesis and its underlying mechanism remains largely unknown. In this study, mouse embryo fibroblasts 3T3-L1 cells were exposed to β-CYP, and the cell viability, intracellular reactive oxygen species (ROS) level, autophagy, and adipogenesis were assessed to investigate the roles of oxidative stress and autophagy in the toxic effects of β-CYP on adipogenesis. The results demonstrated that treatment with 100 μΜ β-CYP elevated the ROS level, decreased mitochondrion membrane potential, stimulated autophagy, and enhanced the adipogenesis induced by the mixture of insulin, dexamethasone, and 3-isobutyl-1-methylxanthine. However, co-treatment with N-acetyl-L-cysteine partially blocked the abovementioned effects of β-CYP in 3T3-L1 cells. In addition, co-treatment with rapamycin, an autophagy agonist, enhanced the inductive effect of β-CYP on adipogenesis, whereas co-treatment with 3-methyladenine blocked the enhancement of adipogenesis caused by β-CYP. Moreover, β-CYP also altered the microenvironment of 3T3-L1 cells to an adipogenesis-friendly one by reducing the extracellular expression of miR-34a, suggesting that the culture media of β-CYP-treated 3T3-L1 cells could shift macrophages to M2 type. Taken together, the data obtained in the present study demonstrated that β-CYP promoted adipogenesis via oxidative stress-mediated autophagy disturbance, and it caused macrophage M2 polarization via the alteration of miR-34a level in the microenvironment. The study demonstrated the adipogenesis-promoting effect of β-CYP and unveiled the potential mechanism.</jats:p>

Obesogens: How They Are Identified and Molecular Mechanisms Underlying Their Action

“…Like other pyrethroids (synthetic relatives of the naturally occurring pesticide pyrethrin), bCYP is an EDC and has been found in humans. High concentrations of bCYP (concentrations of 25, 50, and 100 mM) promoted adipogenesis in 3T3-L1 cells (127).…”

“…Like other pyrethroids (synthetic relatives of the naturally occurring pesticide pyrethrin), βCYP is an EDC and has been found in humans. High concentrations of βCYP (concentrations of 25, 50, and 100 μM) promoted adipogenesis in 3T3-L1 cells ( 127 ). Mechanistically, β-CYP acts on 3T3-L1 by increasing the reactive oxygen species within cells via binding to the mitochondrial respiration chain complex 1.…”

Novel perspectives on autophagy-oxidative stress-inflammation axis in the orchestration of adipogenesis

“…There may exist other pathways linking autophagy and oxidative stress. For instance, β-cypermethrin promoted adipogenesis via oxidative stress-mediated autophagy disturbance, and it caused macrophage polarization by mediating miR-34a ( 115 ). Arsenite treatment induces oxidative stress by decreasing UCP1 expression.…”

The Emerging Roles of Autophagy in Human Diseases

“…For instance, CEBPB/C/EBPβ facilitates adipogenesis via activating ATG4B and promoting autophagy [ 360 ]. β-Cypermethrin promotes adipogenesis through inducing autophagy and shaping a microenvironment that is suitable for adipogenesis [ 361 ]. However, autophagy is critical and most active only during the initial stage of adipocyte differentiation but not in the later stage [ 362 ].…”