Chronic Exposure to Environmental Level Phenanthrene Induces Non-Obesity-Dependent Insulin Resistance in Male Mice.

Abstract

Epidemiological evidence shows that the body burden of polycyclic aromatic hydrocarbons (PAHs) is related to the disruption of glucose homeostasis. However, the contribution of PAHs to the development of diabetes remains poorly documented. In the current work, male Kunming mice received phenanthrene (Phe) (5, 50, and 500 ng/kg) by gavage administration once every 2 days for 28 weeks. The significant elevation of homeostasis model assessment-insulin resistance (HOMA-IR) and HOMA-β cell, accompanied by hyperinsulinemia, indicated the occurrence of insulin resistance. The suppression of the insulin receptor signaling pathway in skeletal muscle might be responsible for glucose intolerance. Under the nonobese state, the serum levels of resistin, tumor necrosis factor-α, and interleukin-6 were elevated, whereas the levels of adiponectin were reduced. These changes in adipocytokine levels were consistent with their transcription in white adipose tissue. The promoter methylation levels of Retn (encoding resistin) and Adipoq (encoding adiponectin) were inversely correlated with their mRNA levels, indicating that Phe exposure could cause the disruption of adipocytokine secretion via epigenetic modification. The results would be helpful for understanding the pathogenesis in the development of T2DM caused by nonobesogenic pollutants.