First, rapid and differential changes in the gut microbiota in obese-prone (OP) and obese-resistant (OR) mice fed on a high-fat diet (HFD) might cause differential efficiencies in fatty acid harvesting leading to changes in systemic fatty acid concentrations that in turn affect POMC expression and processing.
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.
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.
This study demonstrates that TCS exposure during early/mid-gestation through the hypermethylation of the POMC promoter reduces the expression of anorexigenic neuropeptides to cause the postnatal hyperphagic obesity, leading to metabolic syndrome in adulthood.
Recent human studies suggest POMC DNA methylation is influenced by maternal nutrition in early pregnancy and associated with childhood and adult obesity.
In conclusion, desacetyl-α-MSH and α-MSH play salutary roles in sexually dimorphic melanocortin obesity and sexually dimorphic HF diet-induced C57BL/6J obesity.
In association with these, male and female mice were protected from HFD-induced obesity, showing decreased feeding and increased energy expenditure that were associated with changes in the synaptic input organization and activation of the anorexigenic hypothalamic POMC neurons and astrogliosis.
Previous studies have shown that congenital Rpgrip1l hypomorphism in murine proopiomelanocortin (Pomc) neurons causes obesity by increasing food intake.
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.
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.
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.
Selective deletion of LEPR in these neurons with the Cre-loxP system, however, has previously failed to recapitulate, or only marginally recapitulated, the obesity and diabetes that are seen in LEPR-deficient Lepr <sup>db/db</sup> mice, suggesting that AGRP or POMC neurons are not directly required for the effects of leptin in vivo<sup>8-10</sup>.
To further define the MC4R pathway and its potential impact on obesity, we tested associations between body mass index (BMI) and LoF mutation burden in the POMC, PCSK1, and LEPR genes in various populations.
We discuss the pathogenesis of this condition with emphasis on the crosstalk between hypothalamic and peripheral signals in the development of obesity and the POMC-melanocortin 4 receptors system as a target for therapeutic intervention.
Based on these data we propose that there is potential to exploit the naturally occurring POMC-derived peptides to treat obesity but this relies on first understanding the specific function(s) for desacetyl-α-MSH and α-MSH.
These results demonstrate that POMC SGK1/FOXO3 signaling mediates glucocorticoid-increased adiposity, providing new insights into the mechanistic link between glucocorticoids and fat accumulation and important hints for possible treatment targets for obesity.
Herein, we show that mice lacking p53 in agouti-related peptide (AgRP), but not proopiomelanocortin (POMC) or steroidogenic factor-1 (SF1) neurons, are more prone to develop diet-induced obesity and show reduced brown adipose tissue (BAT) thermogenic activity.
Elevated TCPTP in POMC neurons in obesity and/or after fasting repressed insulin signaling, the activation of POMC neurons by insulin and the insulin-induced and POMC-mediated repression of HGP.