Protective Effect of Leptin and Ghrelin against Toxicity Induced by Amyloid-β Oligomers in a Hypothalamic cell Line

In addition to cognitive decline, Alzheimer's disease (AD) patients also exhibit an unexplained weight loss that correlates with disease progression. In young and middle‐aged AD patients, large amounts of amyloid‐β (Aβ) deposits were observed in the hypothalamus, a brain region involved in the control of feeding and body weight through the action of peripheral metabolic peptides, which have recently been shown to have neuroprotective effects. Moreover, levels of peripheral metabolic peptides, such as leptin and ghrelin, are changed in AD patients. The present study aimed to investigate the role of Aβ peptide in the survival of hypothalamic cells and to explore the receptor‐mediated protective effect of leptin and ghrelin against Aβ‐induced toxicity in these cells. Using the mHypoE‐N42 cell line, we demonstrated for the first time that oligomeric Aβ is toxic to hypothalamic cells, leading to cell death. It was also demonstrated that leptin and ghrelin protect these cells against AβO‐induced cell death through the activation of the leptin and ghrelin receptors, respectively. Furthermore, ghrelin and leptin prevented superoxide production, calcium rise and mitochondrial dysfunction triggered by AβO. Taken together, these results suggest that peripheral metabolic peptides, in particular leptin and ghrelin, might be considered as preventive strategies for ameliorating hypothalamic alterations in AD.