New mechanistic insights on the metabolic-disruptor role of chlorpyrifos in apoE mice: a focus on insulin- and leptin-signalling pathways

Peris-Sampedro, Fiona (author): Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology

Blanco, J. (author)

Cabre, M. (author)

Basaure, P. (author)

Guardia-Escote, L. (author)

Domingo, J. L. (author)

Sanchez, D. J. (author)

Colomina, M. T. (author)

(creator_code:org_t)

2018-02-05
2018
English.
In: Archives of Toxicology. - : Springer Science and Business Media LLC. - 0340-5761 .- 1432-0738. ; 92:5, s. 1717-1728

Related links:: https://gup.ub.gu.se...; show more...; https://doi.org/10.1...; show less...

Abstract Subject headings

Recently, we have provided evidence, suggesting that mice expressing the human apolipoprotein E3 (apoE3) are more prone to develop an obesity-like phenotype and a diabetic profile when subchronically fed a chlorpyrifos (CPF)-supplemented diet. The aim of the current study was to examine the underlying mechanisms through which CPF alters both insulin- and leptin-signalling pathways in an APOE-dependent manner. Both adult apoE3- and E4-targeted replacement and C57BL/6 mice were exposed to CPF at 0 or 2 mg/kg body weight/day through the diet for 8 consecutive weeks. We determined the expression of JAK2, p-JAK2, STAT3, p-STAT3, SOCS3, IRS-1, p-IRS-1, AKT, p-AKT, GSK3 beta, p-GSK3 beta, and apoE in the liver, as well as hepatic mRNA levels of pon1, pon2, and pon3. CPF markedly disrupted both leptin and insulin homeostasis, particularly in apoE3 mice. Indeed, only CPF-fed apoE3 mice exhibited an increased phosphorylation ratio of STAT3, as well as increased total SOCS3 protein levels. Similarly, the exposure to CPF drastically reduced the phosphorylation ratio of both AKT and GSK3 beta, especially in apoE3 mice. Overall, CPF reduced the expression of the three pon genes, principally in C57BL/6 and apoE3 mice. These results provide notable mechanistic insights on the metabolic effects of the pesticide CPF, and attest the increased vulnerability of apoE3 carriers to its metabolic-disruptor role.

MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

By the author/editor: Peris-Sampedro, ...; Blanco, J.; Cabre, M.; Basaure, P.; Guardia-Escote, ...; Domingo, J. L.; show more...; Sanchez, D. J.; Colomina, M. T.; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Endocrinology an ...

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