Preventive Impact of Long-Term Ingestion of Chestnut Honey on Glucose Disorders and Neurodegeneration in Obese Mice

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.

A Review of the Health Benefits of Food Enriched with Kynurenic Acid

“…This creates a unique opportunity to verify whether the consumption of chestnut honey brings health benefits to humans. In fact, there are scientific reports on the effects of chestnut honey on diseases modeled in laboratory animals [ 127 , 128 , 129 , 130 , 131 ] ( Table S14 ). Interestingly, similar to KYNA, chestnut honey administered by the alimentary route counteracts the effects of a high-fat diet in mice and also has an antiulcer effect in the alcohol model of the disease in rats [ 127 , 128 ].…”

“…In fact, there are scientific reports on the effects of chestnut honey on diseases modeled in laboratory animals [ 127 , 128 , 129 , 130 , 131 ] ( Table S14 ). Interestingly, similar to KYNA, chestnut honey administered by the alimentary route counteracts the effects of a high-fat diet in mice and also has an antiulcer effect in the alcohol model of the disease in rats [ 127 , 128 ]. Moreover, it was found to enhance the healing of CCl4-induced liver damage in rats [ 129 ].…”

Insulin and Its Key Role for Mitochondrial Function/Dysfunction and Quality Control: A Shared Link between Dysmetabolism and Neurodegeneration

“…Hence, dysregulation of GLUT4 could, at least in part, explain the comorbidity of T2D and AD diseases. Furthermore, several findings indicate that insulin resistance in the brain of obese mice can be inhibited or reversed by feeding animals with a diet in which regular intake of pistachio or honey or natural dietary supplements are consumed [ 87 , 88 , 89 , 90 , 91 ]. Diet, indeed, has become the object of investigation concerning cognitive aging and neurodegenerative disease.…”

Long-Term Ingestion of Sicilian Black Bee Chestnut Honey and/or D-Limonene Counteracts Brain Damage Induced by High Fat-Diet in Obese Mice

“…More specifically, our recent investigation demonstrated the ability of honey consumption to prevent HFD-dependent neuronal injury. In particular, a 16-week-intake of Sicilian black bee chestnut honey, which is particularly rich in kaempferol and quercetin [ 22 ], prevented peripheral and central insulin resistance and neuroinflammation in mice fed with a hyperlipidic diet [ 23 ]. This neuroprotective effect proved to be mainly due to the positive modulation of brain genes involved in insulin signaling, neuroinflammation and apoptosis [ 23 ].…”

“…In particular, a 16-week-intake of Sicilian black bee chestnut honey, which is particularly rich in kaempferol and quercetin [ 22 ], prevented peripheral and central insulin resistance and neuroinflammation in mice fed with a hyperlipidic diet [ 23 ]. This neuroprotective effect proved to be mainly due to the positive modulation of brain genes involved in insulin signaling, neuroinflammation and apoptosis [ 23 ]. However, it remains to be investigated whether the long-term ingestion of honey is able to revert obesity-related metabolic dysfunctions and related neurodegeneration.…”