Alteration of ghrelin–neuropeptide Y network in obese patients with polycystic ovary syndrome: role of hyperinsulinism

Romualdi, Daniela; Marinis, Laura De; Campagna, Giuseppe; Proto, Caterina; Lanzone, Antonio; Guido, Maurizio

doi:10.1111/j.1365-2265.2008.03204.x

Cited by 27 publications

(24 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However in severely obese, polycystic ovarian syndrome (PCOS) patients it has been observed that this inverse relationship between leptin and NPY is lost. NPY levels are often elevated, yet some PCOS patients exhibit equal to or higher than expected leptin levels likely due to endocrine dysregulation [41][42][43] which is consistent with our observations in this study. Furthermore, NPY response to ghrelin is also defective in PCOS patients [41].…”

Section: Doi: 107243/2050-0866-2-23supporting

confidence: 91%

Peripartum changes in the orexigenic CNS peptide neuropeptide-Y in gestational diabetics

Anchan

Lindsey²,

Newton³

et al. 2013

J Diab Res Clin Met

View full text Add to dashboard Cite

Background: Development of relative insulin resistance during pregnancy is a normal physiologic change related to placental lactogen and pregnancy-associated elevated lipid concentrations. Several studies have investigated the role of tissue response, tyrosine kinase insulin receptor phosphorylation, and other cytokines that might contribute to development of such resistance. In this study, we specifically investigate the accompanying changes in concentrations of the orexigenic neurotransmitter neuropeptide Y (NPY) during pregnancy with the development and resolution of insulin resistance in gestational diabetics. Given that increased NPYergic activity is associated with increased eating behavior and body weight, we hypothesize levels of the central nervous system (CNS) peptide NPY will shift, along with other factors such as adiponectin, leptin, and ghrelin, in the development and resolution of gestational diabetes mellitus. Methods: Antepartum and postpartum plasma concentrations of NPY, leptin, ghrelin, tumor necrosis factor-alpha, glucose, and insulin were measured in gravid patients that were healthy (N=22), class A1 and A2 gestational diabetics (N=8), or type 2 diabetics (N=4). Homeostatic Model Assessment of insulin resistance was also calculated. Data was analyzed using a t-test and considered significant with p<0. 05. Results: We demonstrate that during the third trimester, class A2 gestational diabetics display an elevated NPY concentration. This elevated NPY begins to resolve immediately postpartum, normalizing by the patient's 6 week postpartum visit. The associated Homeostatic Model Assessment of insulin resistance index (HOMA) is consistent with these observations showing a concomitant elevation of HOMA intrapartum with improved insulin resistance within 24 hours postpartum. Discussion: Collectively, these results suggest a role for central nervous system involvement in the development of insulin resistance during gestational diabetes. Additionally, rising NPY levels during pregnancy may warrant routine patient surveillance for the development of occult insulin resistance and the obstetrical management of the same.

show abstract

Section: Doi: 107243/2050-0866-2-23supporting

confidence: 91%

Peripartum changes in the orexigenic CNS peptide neuropeptide-Y in gestational diabetics

Anchan

Lindsey²,

Newton³

et al. 2013

J Diab Res Clin Met

View full text Add to dashboard Cite

show abstract

“…Compared to controls, PCOS women had a significantly suppressed neuropeptide Y response to injected ghrelin, as the response has restored after treatment with metformin and significant insulin reduction. In this experimental setting, leptin has undergone no significant changes [289]. Obviously, hyperinsulinaemia is the factor which exerts effect on the ghrelin-neuropeptide Y relation.…”

Section: Ghrelin's Role In Processes Of Reproduction and Pcosmentioning

confidence: 85%

“…In contrast, Romualdi et al [145] demonstrated that in basal conditions, obese PCOS women exhibited lower NPY levels than obese controls. Ghrelin injection markedly increased NPY in controls, whereas PCOS women showed a deeply blunted NPY response to the stimulus.…”

Section: Npy and Reproductive Functionmentioning

confidence: 87%

“…The authors conclude that hyperinsulinaemia seems to play a pivotal role in the alteration of NPY response to ghrelin in obese PCOS women. This derangement could be implicated in the pathophysiology of obesity in these patients [145]. The limitations of this very interesting study on the ghrelin-NPY relationship in PCOS is the small number of patients (seven obese, hyperinsulinaemic subjects with PCOS and seven obese control women) and the data need further purposeful investigation.…”

Section: Npy and Reproductive Functionmentioning

confidence: 93%

“…Romualdi et al [289] gave more detailed evaluation of ghrelin and polypeptide YY responses following oral load with a test meal (527 kcal, distributed by contents in 24.1% fats, 54.4% carbohydrates and 21.5% proteins) in women with PCOS. Low baseline ghrelin levels and reduced suppression after meals, more pronounced in the obese than in the lean patients was shown.…”

Section: Ghrelin's Role In Processes Of Reproduction and Pcosmentioning

confidence: 99%

See 2 more Smart Citations

Appetite Regulatory Peptides and Insulin Resistance

Orbetzova¹

2012

Insulin Resistance

View full text Add to dashboard Cite

In addition to leptin and insulin, receptors for ghrelin are also located on arcuate AgRP/NPY neurons, which are activated by central ghrelin administration. Furthermore, peripheral ghrelin administration activates neurons in the ARC and AgRP and NPY have been demonstrated to be requisite mediators of the hyperphagia induced by systemic ghrelin [11]. So, meal-generated satiety signals from the GI tract do interact with longer-term adiposity signals, such as insulin and leptin in energy balance [8].NPY is one of the most abundant peptides of the hypothalamus and one of the most potent orexigenic factors. The majority of neurons expressing NPY in the hypothalamus are found within the ARC and most co-express AgRP [14]. Synthesis and release of NPY are both regulated by leptin binding to its hypothalamic receptor. NPY links afferents reflecting the nutritional status of the organism from endocrine, gastrointestinal, and central and peripheral nervous systems to effectors of energy intake and expenditure [15]. NPY stimulates appetite inducing hyperphagia, increase of fat depots, decrease of thermogenesis, and suppression of sympathetic activity. NPY is known to be involved in other physiological functions, such as cardiovascular regulation, affective disorder, memory retention, neuroendocrine control. When leptin levels increase after food intake, the latter binds to its receptors in the hypothalamus which leads to discontinuation of NPY secretion [5,16]. The decrease of NPY concentration in obesity probably plays a role of a counterregulatory factor intended to prevent further weight gain. Thus, NPY becomes one of the main regulators of food intake, body weight and energy expenditure.Ghrelin is a fast-acting hormone, seemingly playing a role in meal initiation. Secreted predominantly from the stomach, ghrelin is the natural ligand for the growth hormone secretagogue-receptor (GHS-R) in the pituitary gland, thus fulfilling the criteria of a brain- gut peptide [5,6]. Although the majority of ghrelin is produced peripherally, there are ghrelin immunoreactive neurons within the hypothalamus that have terminals on hypothalamic NPY/AgRP, POMC and corticotropin releasing hormone (CRH) neurons [17], as well as orexin fibres in the LHA [18]. It was found that ghrelin acts to promote appetite in two ways-directly, by depolarizing the orexigenic NPY/AgRP neurons, and indirectly, by increasing the tonic inhibition exerted by the NPY/AgRP neurons over the anorexigenic POMC/CART neurons. Both of these ultimately enhance appetite [4,17,18]. The ability of ghrelin to increase food intake and body weight is mediated through the stimulation of NPY production in the hypothalamic ARC, where it antagonizes the inhibitory effect on NPY secretion displayed by leptin and insulin [19].The purpose of this chapter is to provide background information on the relationship between the main appetite regulatory peptides NPY and ghrelin, and insulin resistance. The role of NPY and ghrelin in food intake and body weight control in humans, and their ...

show abstract

A 12-week treatment with the long-acting glucagon-like peptide 1 receptor agonist liraglutide leads to significant weight loss in a subset of obese women with newly diagnosed polycystic ovary syndrome

et al. 2015

View full text Add to dashboard Cite

Alteration of ghrelin–neuropeptide Y network in obese patients with polycystic ovary syndrome: role of hyperinsulinism

Abstract: Hyperinsulinaemia seems to play a pivotal role in the alteration of NPY response to ghrelin in obese PCOS women. This derangement could be implicated in the physiopatology of obesity in these patients.

Cited by 27 publications

References 39 publications

Peripartum changes in the orexigenic CNS peptide neuropeptide-Y in gestational diabetics

Peripartum changes in the orexigenic CNS peptide neuropeptide-Y in gestational diabetics

Appetite Regulatory Peptides and Insulin Resistance

A 12-week treatment with the long-acting glucagon-like peptide 1 receptor agonist liraglutide leads to significant weight loss in a subset of obese women with newly diagnosed polycystic ovary syndrome

Contact Info

Product

Resources

About