NaF treatment increases TNF-α and resistin concentrations and reduces insulin signal in rats

The use of fluoridated products has significantly contributed to the reduction in rates of dental caries. However, excessive sodium fluoride (NaF) intake promotes inhibition of glycolysis, decrease in insulin secretion, hyperglycemia, and insulin resistance. Seven-week-old castrated male Wistar rats were used to evaluate the chronic effect of NaF on insulin sensitivity, insulin signal transduction in white adipose tissue (WAT), and plasma TNF-α and resistin concentrations. The animals were randomly divided into two groups: (1) control group (CN); (2) fluoride (F) group, which was treated with NaF in the drinking water and F in the food pellets (estimated total F intake: 4.0 mg/kg bw/day). After 42 days, an intravenous insulin tolerance test (0.75 U/kg), plasma TNF-α and resistin quantification analysis, and insulin receptor substrate (pp185 – IRS-1/IRS-2) tyrosine phosphorylation and IRS-1 serine phosphorylation status tests in WAT were performed. The chronic treatment with F promoted: (1) decrease in pp185 (IRS-1/IRS-2) tyrosine phosphorylation status in the WAT; (2) increase in IRS-1 serine phosphorylation status in the WAT; (3) increase in plasma concentrations of TNF-α and resistin; and (4) decrease in insulin sensitivity.

Insulin-stimulated tyrosine phosphorylation status of pp185 (IRS-1/IRS-2) and insulin-stimulated serine phosphorylation status of IRS-1 in white adipose tissue (WAT) of control and F groups, before (−) and after (+) insulin infusion. In A and B, typical autoradiogram of insulin-stimulated tyrosine phosphorylation status of pp185 (IRS-1/IRS-2) and serine phosphorylation status of IRS-1 in WAT, respectively. C and D show data after insulin infusion, expressed in arbitrary units per μg of protein (mean ± SEM, n = 6). *p < 0.05 compared to control group.Figure optionsDownload as PowerPoint slideHighlights
► Decrease in pp185 tyrosine phosphorylation status in the white adipose tissue.
► Increase in IRS-1 serine phosphorylation status in the white adipose tissue.
► Increase in plasma concentrations of TNF-α and resistin.
► Decrease in insulin sensitivity.