Abstract
The purpose of the present study was to evaluate the impact of long-term honey ingestion on metabolic disorders and neurodegeneration in mice fed a high-fat diet (HFD). Three groups of mice were fed with a standard diet (STD), HFD or HFD supplemented with honey (HFD-H) for 16 weeks. Biochemical, histological, Western blotting, RT-PCR and Profiler PCR array were performed to assess metabolic parameters, peripheral and central insulin resistance and neurodegeneration. Daily honey intake prevented the HFD-induced glucose dysmetabolism. In fact, it reduced plasma fasting glucose, insulin and leptin concentrations and increased adiponectin levels. It improved glucose tolerance, insulin sensitivity and HOMA index without affecting plasma lipid concentration. HFD mice showed a significantly higher number of apoptotic nuclei in the superficial and deep cerebral cortex, upregulation of Fas-L, Bim and P27 (neuronal pro-apoptotic markers) and downregulation of Bcl-2 and BDNF (anti-apoptotic factors) in comparison with STD- and HFD-H mice, providing evidence for honey neuroprotective effects. PCR-array analysis showed that long-term honey intake increased the expression of genes involved in insulin sensitivity and decreased genes involved in neuroinflammation or lipogenesis, suggesting improvement of central insulin resistance. The expressions of p-AKT and p-GSK3 in HFD-H mice, which were decreased and increased, respectively, in HFD mouse brain, index of central insulin resistance, were similar to STD animals supporting the ability of regular honey intake to protect brain neurons from insulin resistance. In conclusion, the present results provide evidence for the beneficial preventative impact of regular honey ingestion on neuronal damage caused by HFD.
Highlights
The excessive long-term ingestion of a high-fat diet (HFD) alters body homeostasis, and it participates in the pathogenesis of neurodegeneration [9,10,11], which is responsible for impairment of cognitive functions in rodents [11]
HFD supplemented with honey (HFD-H) mice was significantly higher than standard diet (STD) mice, but no difference was observed when compared HFD-H to HFD
The major findings from the present study suggest that honey ingestion effectively attenuates obesity-related peripheral and central insulin resistance
Summary
Health Organization has stated that they will become the worldwide second reason of death by the middle of the 21st century after cancer [1]. They include diverse pathological conditions, among which Alzheimer’s and Parkinson’s diseases are the most prevalent ones [2]. Neurodegeneration is characterized by loss of specific neurons, leading to progressive dysfunctions of the central nervous system. The various components of metabolic syndrome (dyslipidemia, obesity, hyperglycemia, insulin resistance and hypertension) cause wide-ranging effects, some of which affect the central nervous system (CNS), and they may result in neurodegenerative diseases [8]. The excessive long-term ingestion of a high-fat diet (HFD) alters body homeostasis, and it participates in the pathogenesis of neurodegeneration [9,10,11], which is responsible for impairment of cognitive functions in rodents [11]
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