Thus, the aim of the present study is to verify the influence of LEPR polymorphism (rs2767485) on serum orexigenic (NPY, MCH and AgRP) and anorexigenic (Leptin and α-MSH) neuropeptides levels among obese adolescents submitted to 1year of multicomponent weight loss therapy.
In obesity, the activated innate immune system leads to increased interleukin (IL)-1β, which is known to stimulate the release of adrenocorticotropin hormone (ACTH).
Earlier pharmacological and POMC gene transfer studies demonstrate that melanocortin activation in either site alone improves insulin sensitivity and reduces obesity.
Patients with rare defects in the gene encoding proopiomelanocortin (POMC) have extreme early-onset obesity, hyperphagia, hypopigmentation, and hypocortisolism, resulting from the lack of the proopiomelanocortin-derived peptides melanocyte-stimulating hormone and corticotropin.
The aim of this work was a comparative study of the localization and number of leptin receptors (LepR), types 1 and 2 dopamine receptors (D<sub>1</sub>R, D<sub>2</sub>R), 5-HT<sub>1B</sub>R and 5-HT<sub>2C</sub>R on the POMC-neurons and the expression of the genes encoding them in the ARC of the normal and diet-induced obese (DIO) rodents and the agouti mice (A <sup>y</sup> /a) with the melanocortin obesity.
Consistent with a pivotal role of the melanocortin system in the control of energy homeostasis, disruption of the Pomc gene causes hyperphagia and obesity.
Few genes such as leptin, leptin receptor encoded by the db (diabetes), pro-opiomelanocortin, AgRP and NPY and melanocortin-4 receptors and insulin-induced gene 2 were linked to obesity.
Our study advances the understanding of the molecular nature of hypothalamic POMC neurons and will be useful to determine whether polymorphisms in POMC regulatory regions play a role in the predisposition to obesity.
A fluorescence resonance energy transfer study showed an interaction between GTRAP3-18 and POMC <i>in vitro</i> These findings suggest that activation of the melanocortin pathway by modulating GTRAP3-18/POMC interaction could be an alternative strategy for obesity and/or type 2 diabetes.-Aoyama, K., Bhadhprasit, W., Watabe, M., Wang, F., Matsumura, N., Nakaki, T. GTRAP3-18 regulates food intake and body weight by interacting with pro-opiomelanocortin.
The availability of a large extended pedigree provided the opportunity to address whether loss of one copy of the POMC gene was sufficient to alter obesity risk.
POMC has also been identified as one of the candidate loci for polycystic ovary syndrome (PCOS) which features hyperandrogenism and some prevalence of obesity in patients.
In particular, both obesity and aging are associated with rewiring of a principal brain pathway modulating energy homeostasis, promoting reduced activity of satiety pro-opiomelanocortin (POMC) neurons within the arcuate nucleus of the hypothalamus (ARC).
A 71-year-old female with general fatigue, central obesity and impaired glucose tolerance was diagnosed with Cushing's syndrome due to elevated ACTH (192.9 pg/mL; normal range, 7.2-63.3 pg/mL), cortisol (73.1 μg/dL; 6.4-21.0 μg/dL) and 24-h urinary free cortisol (UFC) (6160 μg/day; 11.2-80.3 μg/day) levels.
Although the primary cause of obesity is unknown, there is significant effort to understand the role of the central melanocortin pathway in the brain as it has been shown that deficiency of proopiomelanocortin (POMC) [10,11] and melanocortin 4 receptors (MC4R) [12-15] in both rodents and humans results in severe hyperphagia and obesity [16-23].
These findings further support the hypothesis that POMC-derived peptides might have a role in the control of peripheral glucose metabolism and suggest that disruption of central POMC secretion might represent an additional link between type 2 diabetes and obesity.
In this study, we did not find association between the frequently studied ENPP1 K121Q variant, nor SNPs in the MCR or POMC genes and obesity or type 2 diabetes.
These findings show that males are more responsive to the pleiotropic actions of N/OFQ at anorexigenic VMN SF-1/ARC POMC synapses, and this responsiveness can be further enhanced under conditions of diet-induced obesity/insulin resistance.
The aim of this study was to investigate the possible associations of defined variability in leptin, leptin receptor, adiponectin, proopiomelanocortin and ghrelin genes with food preferences in the obese and non-obese Czech population and evaluate their potential as the obesity susceptibility genes.
The genes at these loci include agouti, which encodes a molecule that antagonizes the binding of alpha melanocyte-stimulating hormone to its receptor; fat, which encodes carboxypeptidase E; tubby, which encodes a putative phosphodiesterase; obese, which encodes a circulating satiety protein; and diabetes, which encodes the receptor for the obese gene product.