Remodeling on adipocytic physiology of organophosphorus esters in mature adipocytes

Liu, Ying; Le, Yifei; Xu, Mengting; Wang, Wanyue; Chen, Hang; Zhang, Quan; Wang, Cui

Remodeling on adipocytic physiology of organophosphorus esters in mature adipocytes

2022

The emerging endocrine disruption chemicals organophosphate esters (OPEs) pose high risk of metabolic disruption. However, limited information is available on physiological disturbance of OPEs on adipose, a major endocrine and metabolic organ. In this study, physiological change was investigated after exposing 3T3-L1fully differentiated adipocytes to six OPEs at non-cytotoxic concentrations. We found two chlorinated-OPEs (tris-(2-chloro-1-(chloromethyl) ethyl) phosphate (TDCPP) and tris(2-chloroisopropyl) phosphate (TCPP)) and two alkyl-OPEs (tributyl phosphate (TBP) and tris (2-butoxyethyl) phosphate (TBEP)) induced inflammation-like adipokines (chemoattractant protein 1 and interleukin-6), respectively. Increment of insulin-resistance-related hormones (resistin and leptin) were observed under TDCPP, TCPP, and TBP exposure. Functional and mechanistic investigation revealed that all of the compounds inhibited lipolysis at basal level through dephosphorylated HSLˢᵉʳ⁵⁶³, the rate limiting enzyme of lipolysis. Triphenyl phosphate (TPhP), tricresyl phosphate (TCP), TDCPP, TBP and TBEP enhanced glucose uptake at both basal and insulin-stimulated status. We evidenced that impact was independent of the classical pIRSˢᵉʳ⁶³⁹/pAKTˢᵉʳ⁴⁷³ nor the insulin-independent AMPK pathway. The elevated mRNA of slc2a4 and its transcriptional factor LXRα may, at least partially, explain for the increase of glucose uptake. Given the focus within the endocrine disruption on glands, it would be prudent not to ignore endocrinal impact on adipocytes.

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