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

Abstract

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.

Effects of Zinc Supplementation on Inflammatory and Cognitive Parameters in Middle-Aged Women with Overweight or Obesity

“…It has been demonstrated that even low doses of Zn, supplemented for 4 weeks, can reduce neuroinflammation and memory deficits resulting from diet-induced obesity [26]. In line with these findings, Hafez et al (2023) showed that Zn supplementation at both low and high doses, for the same 4-week period, was able to reverse the reduction in brain-derived neurotrophic factor (BDNF) levels in the hippocampus of obese mice [44]. In addition, a positive correlation between serum levels of BDNF and zinc has been previously described [42].…”

“…On the other hand, preclinical studies conducted in animal models have consistently yielded evidence regarding the advantages of Zn supplementation in ameliorating metabolic outcomes associated with obesity [26,44,61]. Obese rats supplemented with Zn showed an improvement in blood glucose levels, triglycerides, and a reduction in leptin resistance when compared to controls that did not receive Zn treatment [44].…”

The Effects of Zinc and Selenium Co-Supplementation on Resting Metabolic Rate, Thyroid Function, Physical Fitness, and Functional Capacity in Overweight and Obese People under a Hypocaloric Diet: A Randomized, Double-Blind, and Placebo-Controlled Trial

“…Numerous systematic reviews and meta-analyses have highlighted that Se and Zn supplementation may positively affect many aspects of health in people with or without diseases and pathological conditions [ 24 , 25 , 26 , 27 , 28 ]. Regarding the effects of Zn and Se supplementation on body composition, positive results have been found in some animal studies [ 29 , 30 , 31 , 32 ]. However, according to a systematic review, randomized controlled trials about the effects of the two elements on body composition in people with overweight or obesity are conflicting and have several limitations [ 33 ].…”