Both studies met their primary endpoints and all key secondary endpoints, demonstrating a statistically significant and clinically meaningful effect on weight loss and reductions in insatiable hunger, or hyperphagia, in patients with POMC
and LEPR deficiency obesities.
The company said it is working to advance setmelanotide to its first regulatory submission in POMC
and LEPR deficiency obesities, with a likely timeline of the fourth quarter of 2019 or the first quarter of 2020 for the submission of a rolling NDA.
There were no significance intergroup differences in expression for NPY and POMC
. The reduction in leptin receptor mRNA levels might explain (at least in part) the hyperphagia observed in noise-exposed animals, even though the mRNA expression level of NPY did not differ significantly.
They revealed that when they activated POMC
cells, this also activated nearby AgRP cells.
At PND180, the POMC
immunostaining in the ARC (Figure 6A-C) showed a gender effect ([F.sub.1,21]=37.12) in the controls (+ 100% in C females vs C males, P<0.05) as well as in the SE animals (+ 103% in SE females vs SE males, P<0.05).
In addition to [alpha]-MSH, [beta]-endorphin is produced from POMC
. Beta-endorphin autoinhibits hypothalamic POMC
neurons through their [mu]-opioid receptors (19, 20).
It is well known that delivery and CS alone elicit the profound response of pituitary proopiomelanocortin (POMC
) system, resulting in elevated levels of beta-endorphins and ACTH, which may modify the emotional state of the patients after CS .
The lack of cortisol negative feedback increases hypothalamic CRH, leading to increased pituitary ACTH and melanocyte-stimulating hormone (MSH), both of which are derived from a precursor, proopiomelanocortin (POMC
Furthermore, to our knowledge, it is not established from any genome-wide association studies in literature whether some genes such as FTO, LEP, LEPR, MC4R, NPY2R, and POMC
that have been implicated in higher BMI are located on the same chromosomal region as that of ABO or that ABO gene exerts regulatory control over them.
ACTH, the product of proopiomelanocortin gene (Pomc
), is secreted from the corticotroph cells of the anterior pituitary.
These genes encoded proteins primarily involved in integrin signalling pathways (ACTA2, PIK3C2G, COL4A6, CAV1, LAMA1, FN1, and ITGA8), regulation of hormone levels (NR5A1, TIPARP, ACE, CRYM, CGA, ALDH1A1, TBX3, POMC
, GHRH, and ALDH6), camera-type eye development (TGFBR2, BMP4, FABP7, STRA6, SIX6, and WNT6), blood vessel development (Figure S1, goo.gl/tC9GTZ), and regulation of cellular response to growth factor stimulus (see Figure 2).
Kaji, "The acute anorexic effect of liraglutide, a GLP-1 receptor agonist, does not require functional leptin receptor, serotonin, and hypothalamic POMC
and CART activities in mice," Diabetes Research and Clinical Practice, vol.