Hormonal Regulators of Appetite

Abstract

Obesity is a significant cause of morbidity and mortality worldwide. There has been a significant worsening of the obesity epidemic mainly due to alterations in dietary intake and energy expenditure. Alternatively, cachexia, or pathologic weight loss, is a significant problem for individuals with chronic disease. Despite their obvious differences, both processes involve hormones that regulate appetite. These hormones act on specific centers in the brain that affect the sensations of hunger and satiety. Mutations in these hormones or their receptors can cause substantial pathology leading to obesity or anorexia. Identification of individuals with specific genetic mutations may ultimately lead to more appropriate therapies targeted at the underlying disease process. Thus far, these hormones have mainly been studied in adults and animal models. This article is aimed at reviewing the hormones involved in hunger and satiety, with a focus on pediatrics.

Role of Somatostatin in the Regulation of Central and Peripheral Factors of Satiety and Obesity

“…Leptin acts on DAergic neurons in VTA to suppress feeding and insensitive to palatable food and mice lacking D2R are more sensitive to leptin. These studies further strengthen the concept regarding the role of receptor interaction in obesity and satiety via regulation of different hormonal secretion and release, in response to either central or peripheral input, as described in several pathological conditions via modulation of the signal transduction pathways [15,69,345]. Our recent observations from the colocalization of SST and CB1R in the hypothalamus further suggest possible interaction between SSTR subtypes and CB1R [104].…”

“…Fasting state reduces leptin expression in adipose tissue and its plasma concentrations, which cause the upregulation of the NPY mediated increase in food intake [80]. Similar to leptin, AgRP and NPY expression is reduced and POMC synthesis is increased by insulin with suppressed food intake [15]. Another peripheral hormone, ghrelin, increases food intake and deposition of fat by increasing NPY and AgRP and reducing POMC expression [135].…”

“…Impaired energy regulation, in general, is believed to be the leading cause of obesity. The concept that SST might involve in obesity emerged from the regulation of insulin release [15,16]. Hyperinsulinemia is often seen in obese individuals and postprandial insulin resistance is a critical determinant of obesity in children [17].…”

“…Recent studies have added new information regarding the expression of several other neurotransmitters and peptides and their coexpression with NPY/AgRP and POMC in different regions of hypothalamus.Most neuroendocrine signals and functions displayed by central and peripheral stimuli in regulation and maintenance of appetite are confined in different regions of the hypothalamus. Amongst them ARC is the hypothalamic nuclei that maintains the balance between food intake and energy requirement [15]. ARC remains vulnerable to endocrine signals coming from the rest of the body due to the fenestrated capillaries and close proximity to median eminence [79].…”

Adult exposure to tributyltin affects hypothalamic neuropeptide Y, Y1 receptor distribution, and circulating leptin in mice

“…Thus, the central nervous system plays a fundamental role in food intake regulation integrating neural and endocrine factors. According to this point of view, obesity is not only dependent on the peripheral change in energy homeostasis but can also be considered a ‘neuroendocrine disease’ depending on the alteration of the leptin/hypothalamic circuits controlling food intake (Austin & Marks, ).…”