Human Preadipocytes Differentiated Under Hypoxia Following PCB126 Exposure During Proliferation: Effects on Differentiation, Glucose Uptake and Adipokine Profile

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2023 Sep 28

PMID 37759548

Authors

Zeinab El Amine

Jean-Francois Mauger

Pascal Imbeault

Affiliations

Soon will be listed here.

Abstract

Persistent organic pollutants (POPs) accumulation and hypoxia are two factors proposed to adversely alter adipose tissue (AT) functions in the context of excess adiposity. Studies have shown that preadipocytes exposure to dioxin and dioxin-like POPs have the greatest deleterious impact on rodent and immortalized human preadipocyte differentiation, but evidence on human preadipocytes is lacking. Additionally, hypoxia is known to strongly interfere with the dioxin-response pathway. Therefore, we tested the effects of pre-differentiation polychlorinated biphenyl (PCB)126 exposure at 10 µM for 3 days and subsequent differentiation under hypoxia on human subcutaneous adipocytes (hSA) differentiation, glucose uptake and expression of selected metabolism- and inflammation-related genes. Pre-differentiation PCB126 exposure lowered the adenosine triphosphate (ATP) content, glucose uptake and leptin expression of mature adipocytes but had limited effects on differentiation under normoxia (21% O). Under hypoxia (3% O), preadipocytes ability to differentiate was significantly reduced as reflected by significant decreased lipid accumulation and downregulation of key adipocyte genes such as peroxisome proliferator-activated receptor gamma (PPARγ) and adiponectin. Hypoxia increased glucose uptake and glucose transporter 1 (GLUT1) expression but abolished the adipocytes insulin response and GLUT4 expression. The expression of pro-inflammatory adipokine interleukin-6 (IL-6) was slightly increased by both PCB126 and hypoxia, while IL-8 expression was significantly increased only following the PCB126-hypoxia sequence. These observations suggest that PCB126 does not affect human preadipocyte differentiation, but does affect the subsequent adipocytes population, as reflected by lower ATP levels and absolute glucose uptake. On the other hand, PCB126 and hypoxia exert additive effects on AT inflammation, an important player in the development of chronic diseases such as type 2 diabetes and cardiovascular diseases.

References

Wang B, Wood I, Trayhurn P . Dysregulation of the expression and secretion of inflammation-related adipokines by hypoxia in human adipocytes. Pflugers Arch. 2007; 455(3):479-92. PMC: 2040175. DOI: 10.1007/s00424-007-0301-8. View

Nadal A, Quesada I, Tuduri E, Nogueiras R, Alonso-Magdalena P . Endocrine-disrupting chemicals and the regulation of energy balance. Nat Rev Endocrinol. 2017; 13(9):536-546. DOI: 10.1038/nrendo.2017.51. View

Olsen H, Enan E, Matsumura F . Regulation of glucose transport in the NIH 3T3 L1 preadipocyte cell line by TCDD. Environ Health Perspect. 1994; 102(5):454-8. PMC: 1567145. DOI: 10.1289/ehp.94102454. View

La Merrill M, Emond C, Kim M, Antignac J, Le Bizec B, Clement K . Toxicological function of adipose tissue: focus on persistent organic pollutants. Environ Health Perspect. 2012; 121(2):162-9. PMC: 3569688. DOI: 10.1289/ehp.1205485. View

Wood I, Stezhka T, Trayhurn P . Modulation of adipokine production, glucose uptake and lactate release in human adipocytes by small changes in oxygen tension. Pflugers Arch. 2011; 462(3):469-77. DOI: 10.1007/s00424-011-0985-7. View

Loiola R, Dos Anjos F, Shimada A, Cruz W, Drewes C, Rodrigues S . Long-term in vivo polychlorinated biphenyl 126 exposure induces oxidative stress and alters proteomic profile on islets of Langerhans. Sci Rep. 2016; 6:27882. PMC: 4904407. DOI: 10.1038/srep27882. View

Behan-Bush R, Liszewski J, Schrodt M, Vats B, Li X, Lehmler H . Toxicity Impacts on Human Adipose Mesenchymal Stem/Stromal Cells Acutely Exposed to Aroclor and Non-Aroclor Mixtures of Polychlorinated Biphenyl. Environ Sci Technol. 2023; 57(4):1731-1742. PMC: 9893815. DOI: 10.1021/acs.est.2c07281. View

Linden J, Korkalainen M, Lensu S, Tuomisto J, Pohjanvirta R . Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and leptin on hypothalamic mRNA expression of factors participating in food intake regulation in a TCDD-sensitive and a TCDD-resistant rat strain. J Biochem Mol Toxicol. 2005; 19(3):139-48. DOI: 10.1002/jbt.20065. View

Netzer N, Gatterer H, Faulhaber M, Burtscher M, Pramsohler S, Pesta D . Hypoxia, Oxidative Stress and Fat. Biomolecules. 2015; 5(2):1143-50. PMC: 4496714. DOI: 10.3390/biom5021143. View

10.

van den Dungen M, Murk A, Kok D, Steegenga W . Persistent organic pollutants alter DNA methylation during human adipocyte differentiation. Toxicol In Vitro. 2016; 40:79-87. DOI: 10.1016/j.tiv.2016.12.011. View

11.

Yamazaki K, Suzuki M, Itoh T, Yamamoto K, Kanemitsu M, Matsumura C . Structural basis of species differences between human and experimental animal CYP1A1s in metabolism of 3,3',4,4',5-pentachlorobiphenyl. J Biochem. 2011; 149(4):487-94. DOI: 10.1093/jb/mvr009. View

12.

Lee J, Wada T, Febbraio M, He J, Matsubara T, Lee M . A novel role for the dioxin receptor in fatty acid metabolism and hepatic steatosis. Gastroenterology. 2010; 139(2):653-63. PMC: 2910786. DOI: 10.1053/j.gastro.2010.03.033. View

13.

Nebert D, Dalton T . The role of cytochrome P450 enzymes in endogenous signalling pathways and environmental carcinogenesis. Nat Rev Cancer. 2006; 6(12):947-60. DOI: 10.1038/nrc2015. View

14.

Gadupudi G, Gourronc F, Ludewig G, Robertson L, Klingelhutz A . PCB126 inhibits adipogenesis of human preadipocytes. Toxicol In Vitro. 2014; 29(1):132-41. PMC: 4250299. DOI: 10.1016/j.tiv.2014.09.015. View

15.

Manikandan P, Nagini S . Cytochrome P450 Structure, Function and Clinical Significance: A Review. Curr Drug Targets. 2017; 19(1):38-54. DOI: 10.2174/1389450118666170125144557. View

16.

Lee M, Wu Y, Fried S . Adipose tissue remodeling in pathophysiology of obesity. Curr Opin Clin Nutr Metab Care. 2010; 13(4):371-6. PMC: 3235038. DOI: 10.1097/MCO.0b013e32833aabef. View

17.

Famulla S, Horrighs A, Cramer A, Sell H, Eckel J . Hypoxia reduces the response of human adipocytes towards TNFα resulting in reduced NF-κB signaling and MCP-1 secretion. Int J Obes (Lond). 2011; 36(7):986-92. DOI: 10.1038/ijo.2011.200. View

18.

Chandramouli V, Carter Jr J . Metabolic effects of 2-deoxy-D-glucose in isolated fat cells. Biochim Biophys Acta. 1977; 496(2):278-91. DOI: 10.1016/0304-4165(77)90310-5. View

19.

Weiszenstein M, Musutova M, Plihalova A, Westlake K, Elkalaf M, Koc M . Adipogenesis, lipogenesis and lipolysis is stimulated by mild but not severe hypoxia in 3T3-L1 cells. Biochem Biophys Res Commun. 2016; 478(2):727-32. DOI: 10.1016/j.bbrc.2016.08.015. View

20.

Myre M, Imbeault P . Persistent organic pollutants meet adipose tissue hypoxia: does cross-talk contribute to inflammation during obesity?. Obes Rev. 2013; 15(1):19-28. DOI: 10.1111/obr.12086. View