# Onion Peel Powder's Impact on the Leptin Receptors in the Hippocamp of Obese Rats
## 1 Introduction  
Onion (_Allium cepa_ L.) is a widely available plant that is a source of many natural phytochemicals and bioactive compounds that benefit human health. It contains flavonoids, phytosterols, and saponins, as well as sulfur amino acids and many vitamins and minerals [1]. Over the years, numerous studies have shown many health-promoting properties of onions, including antioxidant [2], anti-inflammatory [3], antimicrobial [4] and anticancer properties [5]. It has been shown that consuming onion extract can lower blood glucoselevels, thereby helping to reduce the risk factors associated with diabetes [6] and [7], and onion may also lower blood cholesterol levels [8]. Flavonoids in onions, including the most active one, quercetin, have a neuroprotective effect, preventing brain aging by inhibiting apoptosis, which induces brain degeneration [9]. It has also been shown that onion can be effective in the prevention and treatment of obesity and have beneficial effects on related comorbidities [10].  
In particular, the properties of dry onion skin, which can be used as a source of valuable nutrients, are of interest. Numerous studies have confirmed that it contains insoluble dietary fiber, minerals (especially calcium and potassium), and highly bio-accessible and in vitro bioavailable flavonoids with well-documented antioxidant and anti-inflammatory properties [11; 12]. Our previous studies indicated that dry onion skin can be a good source of quercetin in pasta. Such an addition gives the pasta antioxidant and potentially anti-inflammatory properties, which are enhanced during the cooking process [13].  
Under physiological conditions, adipose tissue adipocytes secrete adipokines, including leptin (Lep), which, through food centers located in the hypothalamus, inhibits the release of neuropeptide Y, thereby suppressing appetite while promoting energy expenditure by increasing thermogenesis, activating lipolysis, and inhibiting lipogenesis [14]. However, in obesity, blood leptin levels rise, suggesting that individuals with obesity exhibit leptin resistance manifested by a decrease in the number of receptors for leptin or a decline in their sensitivity to the hormone. It was observed that the administration of onion peel extract (at the dose of 0.2 g/100 g diet) in a model of obese rats associated with a high-energy diet reduced body fat (mainly mesenteric) by increasing adiponectin levels while decreasing leptin levels [15].  
Leptin crosses the blood-brain barrier (BBB) and activates leptin receptors (LepRs) that are widely distributed throughout the central nervous system (CNS), including the hippocampus [16; 17]. The hippocampus is a limbic system structure located in the temporal lobe. It controls the transfer of information from short-term to long-term memory, learning, and spatial orientation. The hippocampus is divided into a dorsal part, more involved in cognitive and spatial functions, and a ventral part responsible for emotions [18]. Leptin has the ability to modify the activity of potassium channels in the hippocampus, thereby regulating neuronal excitability. LepRs have been suggested to be involved in the enhancement of synaptic plasticity in the hippocampus and, consequently, in the improvement in hippocampus-dependent behaviors such as spatial learning and memory [19].  
The long-term consumption of a high-fat diet can cause pathological changes in the cellular integrity of the BBB, contributing to leptin resistance in the CNS and, consequently, to structural changes in the brain and cognitive deficits [20]. One of the brain areas adversely affected by leptin resistance is the hippocampus [21]. Among other effects, obesity alters the structure of dendrites in this region, which may indicate that the hippocampus is highly susceptible to metabolic disorders [22]. Therefore, the present study aimed to investigate the effect of dietary supplementation with onion peel powder on hippocampal leptin receptor immunoreactivity and astrocyte density in obese rats fed a high-fat diet for three months.