Abstract
Obesity is known to induce leptin and insulin resistance. Leptin is a peptide hormone synthesized in adipose tissue that mainly regulates food intake. It has been shown that insulin stimulates the production of leptin when adipocytes are exposed to glucose to encourage satiety; while leptin, via a negative feedback, decreases the insulin release and enhances tissue sensitivity to it, leading to glucose uptake for energy utilization or storage. Therefore, resistance to insulin is closely related to leptin resistance. Obesity in middle age has also been related to Alzheimer’s disease (AD). In recent years, the relation between impaired leptin signaling pathway and the onset of AD has been studied. In all this context the role of the blood brain barrier (BBB) is crucial. Slow excitotoxicity happens in AD due to an excess of the neurotransmitter glutamate. Since leptin has been shown to regulate N-methyl-D-aspartate (NMDA) receptors, we want to review the link between these pathological pathways, and how they are affected by other AD triggering factors and its role in the onset of AD.
Highlights
In the last years obesity has changed from a mere aesthetic problem to become into a serious health problem worldwide
We know today that the functions of leptin are many others: it is a growth factor, a permissive factor for puberty, controls metabolism and immune system and is implicated in memory (Margetic et al, 2002; Kelesidis et al, 2010; McGregor and Harvey, 2018a). All these effects are mediated by binding to specific leptin receptors (LepR) expressed in the central nervous system (CNS) as well as in peripheral tissues
A meta-analysis of 15 prospective studies including more than 72000 participants used body mass index (BMI) measures and the authors found that both underweight and obese are related to an increase risk of Alzheimer’s disease (AD) but only in mid-life; high BMI in late-life was not associated with any dementia (Anstey et al, 2011)
Summary
In the last years obesity has changed from a mere aesthetic problem to become into a serious health problem worldwide. The growing incidence caused by a change in eating habits, by an increased consumption of fat and by a substantial reduction in physical activity This nutritional disorder implicates a number of conditions associated with excess weight, such as heart diseases, type 2 diabetes, high blood pressure, different types of cancer, and even neurodegeneration (Friedemann et al, 2012; Odegaard and Chawla, 2013; Hotamisligil, 2017). All these chronic pathologies associated with obesity, englobe the main causes of death and monopolize 80% of healthcare expense (The World Health Organization [WHO], 2019)
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