Ameliorative effects of zinc supplementation on cognitive function and hippocampal leptin signaling pathway in obese male and female rats

Obesity has been associated with cognitive impairments, increasing the probability of developing dementia. Recently, zinc (Zn) supplementation has attracted an increasing attention as a therapeutic agent for cognitive disorders. Here, we investigated the potential effects of low and high doses of Zn supplementation on cognitive biomarkers and leptin signaling pathway in the hippocampus of high fat diet (HFD)-fed rats. We also explored the impact of sex difference on the response to treatment. Our results revealed a significant increase in body weight, glucose, triglycerides (TG), total cholesterol (TC), total lipids and leptin levels in obese rats as compared to controls. HFD feeding also reduced brain-derived neurotrophic factor (BDNF) levels and increased acetylcholinesterase (AChE) activity in the hippocampus of both sexes. The low and high doses of Zn supplementation improved glucose, TG, leptin, BDNF levels and AChE activity in both male and female obese rats compared to untreated ones. Additionally, downregulated expression of leptin receptor (LepR) gene and increased levels of activated signal transducer and activator of transcription 3 (p-STAT3) that observed in hippocampal tissues of obese rats were successfully normalized by both doses of Zn. In this study, the male rats were more vulnerable to HFD-induced weight gain, most of the metabolic alterations and cognition deficits than females, whereas the female obese rats were more responsive to Zn treatment. In conclusion, we suggest that Zn treatment may be effective in ameliorating obesity-related metabolic dysfunction, central leptin resistance and cognitive deficits. In addition, our findings provide evidence that males and females might differ in their response to Zn treatment.

Automated summary

Obesity is associated with cognitive impairments and increases the risk of developing dementia. Zinc supplementation has shown potential as a therapeutic agent for cognitive disorders. The study investigated the effects of low and high doses of zinc supplementation on cognitive biomarkers and leptin signaling pathway in rats fed with a high-fat diet. Results showed that obesity in rats led to increased body weight, glucose levels, and lipid levels, as well as reduced BDNF levels and increased acetylcholinesterase (AChE) activity. Zinc supplementation improved these metabolic abnormalities and cognitive deficits in both male and female obese rats. Furthermore, the study found that males were more vulnerable to weight gain and metabolic alterations, while females were more responsive to zinc treatment. Overall, this study suggests that zinc treatment may be effective in improving obesity-related metabolic dysfunction, central leptin resistance, and cognitive deficits, and that males and females may differ in their response to zinc treatment.