Deregulation of hepatic lipid metabolism associated with insulin resistance in rats subjected to chronic monocrotophos exposure.

Nagaraju, Raju; Joshi, Apurva K. R.; Vamadeva, Sowmya G.; Rajini, Padmanabhan S.

In our previous study, we demonstrated the potential of monocrotophos (MCP), an organophosphorus insecticide (OPI), to induce glucose intolerance, insulin resistance (IR), and dyslipidemia with hyperinsulinemia in rats after chronic exposure. As hyperinsulinemia is likely to exert an impact on hepatic lipid metabolism, we carried out this study to establish the effect of chronic MCP exposure (0.9 and 1.8 mg/kg/day for 180 days) on hepatic lipid metabolism in rats. The state of IR induced by MCP in rats was associated with an increase in the liver lipid content (triglyceride and cholesterol) and expression levels of sterol regulatory element‐binding proteins, PPARγ, acetyl‐CoA carboxylase, and fatty acid synthase in the liver. Similarly, activities of key enzymes (acetyl‐COA carboxylase, fatty acid synthase, lipin 1, malic enzyme, glucose‐6‐phosphate dehydrogenase, and glycerol‐3‐phosphate dehydrogenase), which regulate lipogenesis, were enhanced in livers of pesticide‐treated rats. A strong correlation was observed between insulin levels, hepatic lipid content, and plasma lipid profile in treated rats. Our study suggests that long‐term exposure to OPIs not only has a propensity to induce a state of hyperinsulinemic IR, but it is also associated with augmented hepatic lipogenesis, which may explain dyslipidemia induced by chronic exposure to MCP.

CHOLESTEROL content of food; STEROL regulatory element-binding proteins; LIPID metabolism; INSULIN resistance; ORGANOPHOSPHORUS insecticides; ACETYL-CoA carboxylase; ERGOSTEROL; HYDROXYCHOLESTEROLS

Journal of Biochemical & Molecular Toxicology, 2020, Vol 34, Issue 8, p1

1095-6670

Academic Journal

10.1002/jbt.22506