Remodeling on adipocytic physiology of organophosphorus esters in mature adipocytes. (15th July 2022)

• Record Type: Journal Article
• Authors: Liu, Ying; Le, Yifei; Xu, Mengting; Wang, Wanyue; Chen, Hang; Zhang, Quan; Wang, Cui
• Is Part Of: Environmental pollution. Volume 305(2022)
• Publication Date: 2022-07-15
• Subjects: Organophosphate esters -- Adipocytokine -- Glucose uptake -- Lipolysis; Pollution -- Periodicals; Pollution -- Environmental aspects -- Periodicals; Environmental Pollution -- Periodicals; Pollution -- Périodiques; Pollution -- Aspect de l'environnement -- Périodiques; Pollution -- Effets physiologiques -- Périodiques; Pollution; Pollution -- Environmental aspects; Periodicals; Electronic journals; 363.73
• DOI: 10.1016/j.envpol.2022.119287
• Languages: English
• ISSNs: 0269-7491

Abstract

Abstract: 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 HSL ser563, 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 p IRS ser639 / p AKT ser473 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. Graphical abstract: Image 1 Highlights: The four chlorinated- and alkyl-OPEs induced inflammation-like adipocytokines. The four chlorinated- and alkyl-OPEs trigged leptin and resistin. All tested OPEs inhibit lipolysis at basal level through dephosphorylated HSL ser563 . Glucose disposal by some OPEs was dependent on LXR/glut4.