The Potential Roles of Ghrelin in Metabolic Syndrome and Secondary Symptoms of Alzheimer’s Disease

Abstract

Although the major causative factors of Alzheimer's disease (AD) are the accumulation of amyloid β and hyperphosphorylated tau, AD can also be caused by metabolic dysfunction. The major clinical symptom of AD is cognitive dysfunction. However, AD is also accompanied by various secondary symptoms such as depression, sleep-wake disturbances, and abnormal eating behaviors. Interestingly, the orexigenic hormone ghrelin has been suggested to have beneficial effects on AD-related metabolic syndrome and secondary symptoms. Ghrelin improves lipid distribution and alters insulin sensitivity, effects that are hypothesized to delay the progression of AD. Furthermore, ghrelin can relieve depression by enhancing the secretion of hormones such as serotonin, noradrenaline, and orexin. Moreover, ghrelin can upregulate the expression of neurotrophic factors such as brain-derived neurotrophic factor and modulate the release of proinflammatory cytokines such as tumor necrosis factor α and interleukin 1β. Ghrelin alleviates sleep-wake disturbances by increasing the levels of melatonin, melanin-concentrating hormone. Ghrelin reduces the risk of abnormal eating behaviors by increasing neuropeptide Y and γ-aminobutyric acid. In addition, ghrelin increases food intake by inhibiting fatty acid biosynthesis. However, despite the numerous studies on the role of ghrelin in the AD-related pathology and metabolic disorders, there are only a few studies that investigate the effects of ghrelin on secondary symptoms associated with AD. In this mini review, our purpose is to provide the insights of future study by organizing the previous studies for the role of ghrelin in AD-related pathology and metabolic disorders.

Interfacial Electromigration for Analysis of Biofluid Lipids in Small Volumes

“…Recent research has highlighted the potential role of ghrelin, a survival and hunger hormone, produced by the stomach, and its receptor, growth hormone secretagogue receptor (GHS-R), in the pathogenesis of AD . Studies have suggested that ghrelin and GHS-R may affect lipid metabolism , and contribute to the development and progression of AD. , To further investigate this potential mechanism, we conducted a study using serum samples from GHS-R knockout 5× FAD (familial Alzheimer’s disease) mice and compared them to normal 5× FAD mice.…”

“… 61 Studies have suggested that ghrelin and GHS-R may affect lipid metabolism 62 , 63 and contribute to the development and progression of AD. 61 , 64 To further investigate this potential mechanism, we conducted a study using serum samples from GHS-R knockout 5× FAD (familial Alzheimer’s disease) mice and compared them to normal 5× FAD mice.…”

The Role of Gut Microbiota in the Mechanism of Cognitive Impairment in the Elderly

“…Edible prebiotics contain dietary fiber that promotes the growth of intestinal flora, which is beneficial to the health of the host. Mice treated with the mixture of probiotics and prebiotics had higher levels of gastrointestinal hormones such as ghrelin, leptin, glucagon-like peptide-1 (GLP1) and insulin-stimulating peptide in plasma, among which ghrelin could counteract the memory impairment and synaptic degeneration of AD [66]. Leptin is a neurotrophic factor that exerts neuroprotective effects against Aβ oligomer-induced toxicity in vitro [67].…”

Phoenixin: More than Reproductive Peptide

“…It is worth noting that initial PNX studies focused on its role in the reproduction system [3,4], however no less important effects were observed, e.g., in memory and anxiety [5,6], as well as in glucose and lipid metabolism [7,8]. Some of these bioactivities exhibit features similar to other neuropeptides like orexins [9], ghrelin [10], or kisspeptin [11]. Moreover, in the hypothalamus, PNX is co-expressed with nesfatin-1 [12].…”