Enhanced insulin resistance in diet-induced obese rats exposed to fine particles by instillation.

CONTEXT: Epidemiological studies indicate that diabetes is a sub-population at risk for particulate matter (PM)-associated cardiovascular disease (CVD). Recent animal studies suggested PM might impair glucose tolerance, which may lead to CVD. However, the mechanism remains unclear. OBJECTIVE: To investigate further the PM effect on insulin resistance (IR) in obese and healthy rats. MATERIALS AND METHODS: Male Sprague-Dawley rats were fed with either a high fat diet (HFD) or normal chow diet (NCD) for 6 weeks. Both groups were then further assigned to receive PM(10), PM(2.5) or normal saline (n = 6 per group) by intratracheal instillation (IT) once per week for 3 weeks. Fasting glucose and insulin were measured and homeostasis model assessment-insulin resistance (HOMA-IR) was used to assess IR. Biochemistry tests and lipids profile were examined at sacrifice. The markers of fibrinogen and [nitrate+nitrite], an indicator of nitric oxide (NO) production, C-reactive protein (CRP) and white blood counts (WBCs) in peripheral blood were also determined. RESULTS: Body weight, insulin and HOMA-IR of HFD rats were significantly increased compared with a NCD after 6 weeks. In HFD rats, PM(2.5) increased HOMA-IR after first IT and further increased HOMA-IR at the end of exposure. However, this increase was not observed in NCD rats and after PM(10) exposure. Increased fibrinogen was also noted after chronic PM(2.5) exposure in both HFD and NCD rats. DISCUSSION AND CONCLUSION: Exposure to PM(2.5) enhanced IR in HFD rats but not in NCD rats. Obese subjects with IR may be a susceptible population to particulate air pollution.

Hepatic damage caused by coxsackievirus B3 is dependent on age-related tissue tropisms associated with the coxsackievirus-adenovirus receptor.

Coxsackievirus B (CVB) and enterovirus 71 (EV71) are important causes of severe enteroviral diseases in neonates or young children in Taiwan. CVB can cause fulminant hepatitis, myocarditis or meningoencephalitis. This study was designed to explore the role of coxsackievirus-adenovirus receptor (CAR) in the pathogenesis of CVB3-infected hepatocytes via in vitro and mice studies. CVB3 (CVB3/2630) was isolated from liver tissue of a neonate with fulminant hepatitis. Cell lines A549, HeLa, HEp2 and Huh-7 were maintained in Dulbecco's modified Eagle's medium. Mice progeny 1 or 7 days old were used in the experiments. Viremia was noted in 7-day-old ICR mice 2 h after intraperitoneal injection. The highest viral titers were detected in blood, liver and spleen. Histopathological studies of the liver demonstrated polymorphonuclear cell infiltration, massive hepatic cell necrosis and apoptosis. CAR was expressed more in liver than in other tissues. Expression of CAR decreased with mouse age. Anti-CAR monoclonal antibody prevented infection of Huh-7 cells from CVB3. Furthermore, anti-CAR monoclonal antibody pretreatment can reduce mortality and decrease the level of liver enzymes in CVB3-infected mice. These findings indicate that CAR plays an important role in the initiation of CVB infections and is closely associated with hepatotropism and age-specific susceptibility.