Postnatal overfeeding induces hepatic microRNA-221 expression and impairs the PI3K/AKT pathway in adult male rats.

BACKGROUND

Increasing evidence suggests that postnatal overfeeding induces childhood obesity, which is strongly associated with metabolic syndrome. Insulin resistance is a risk factor for metabolic syndrome. MicroRNA-221 (miR-221) is involved in the development of obesity and has been reported to negatively regulate insulin sensitivity. However, the underlying mechanism remains unclear.

METHODS

Rats raised in small litters (SLs, three pups/dam, n = 10) and normal litters (NLs, 10 pups/dam, n = 10) were used to model early postnatal overfeeding and act as controls, respectively. miR-221 and proteins related to the phosphoinositide 3-kinases (PI3K)/protein kinase B (AKT) pathway were assessed in the liver.

RESULTS

Early postnatal overfeeding significantly increased body weight, visceral fat index, blood glucose, serum triglycerides, and the homeostasis model assessment of insulin resistance at 9 weeks. Real-time polymerase chain reaction (PCR) and western blot analysis revealed that postnatal overfeeding induced insulin receptor and insulin receptor substrate 2 expression, but decreased PI3K and AKT phosphorylation in the liver. Quantitative real-time PCR showed that hepatic miR-221 was significantly overexpressed in the SL group.

CONCLUSIONS

These results indicate that postnatal overfeeding induces hepatic miR-221 overexpression and impairs the PI3K/AKT signal pathway, which may cause insulin resistance.

IMPACT

We first report postnatal overfeeding induces hepatic miR-221 expression. Postnatal overfeeding impairs PI3K/AKT pathway in the liver of adult rats. Postnatal overfeeding induces obesity and high blood glucose. Avoidance of overfeeding during early postnatal life may prevent obesity and T2DM.