Ma Ghatei

Ma Ghatei
Imperial College London | Imperial

About

789
Publications
42,895
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61,143
Citations
Citations since 2017
1 Research Item
11603 Citations
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201720182019202020212022202305001,0001,5002,000
201720182019202020212022202305001,0001,5002,000

Publications

Publications (789)
Article
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Pancreatic polypeptide (PP) is a gut hormone that acts on Y4 receptors to reduce appetite. Obese humans display a reduced postprandial rise in PP and remain fully sensitive to the anorectic effects of exogenous PP. The utility of PP as an antiobesity treatment is limited by its short circulating half-life. Insight into the mechanisms by which PP is...
Article
Full-text available
Objective: Dietary supplementation with fermentable carbohydrate protects against body weight gain. Fermentation by the resident gut microbiota produces short-chain fatty acids, which act at free fatty acid receptor 2 (FFAR2). Our aim was to test the hypothesis that FFAR2 is important in regulating the beneficial effects of fermentable carbohydrate...
Article
Context: Since the discovery of its central role in reproduction, our functional neuroanatomical knowledge of the hypothalamic kisspeptin system is predominantly based on animal studies. Although sex differences in kisspeptin expression have been shown in humans in adulthood, the developmental origin of this sex difference is unknown. Objectives:...
Article
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How potently does the novel hypothalamic stimulator of reproduction, kisspeptin, increase gonadotrophin secretion when compared with GnRH in healthy men? At the doses tested, intravenous administration of either of two major kisspeptin isoforms, kisspeptin-10 and -54, was associated with similar levels of gonadotrophin secretion in healthy men; how...
Article
Full-text available
Kisspeptin (encoded by KISS1) is a crucial activator of reproductive function. The role of kisspeptin has been studied extensively within the hypothalamus but little is known about its significance in other areas of the brain. KISS1 and its cognate receptor are expressed in the amygdala, a key limbic brain structure with inhibitory projections to h...
Article
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Neurokinin B (NKB) is a hypothalamic neuropeptide binding preferentially to the neurokinin 3 receptor. Expression of the gene encoding NKB is elevated in postmenopausal women. Furthermore, rodent studies suggest that NKB signalling may mediate menopausal hot flushes. However, the effects of NKB administration on hot flushes have not been investigat...
Article
Objective Understanding the mechanisms that drive weight loss in a lean population may elucidate systems that regulate normal energy homeostasis. This prospective study of British military volunteers investigated the effects of a 6-month deployment to Afghanistan on energy balance and circulating concentrations of specific appetite-regulating hormo...
Article
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Context and objective: No current biomarker can reliably predict visceral and liver fat content, both of which are risk factors for cardiovascular disease. Vagal tone has been suggested to influence regional fat deposition. Pancreatic polypeptide (PP) is secreted from the endocrine pancreas under vagal control. We investigated the utility of PP in...
Article
Published LC-MS/MS methods are not sensitive enough to quantify endogenous levels of glucagon. An ultra high performance liquid chromatography-MS/MS (SRM) method for the quantitation of endogenous levels glucagon was successfully developed and qualified. A novel 2D extraction procedure was used to reduce matrix suppression, background noise and int...
Article
Neuronal populations that synthesize kisspeptin (KP), neurokinin B (NKB) and substance P (SP) in the hypothalamic infundibular nucleus of humans are partly overlapping. These cells are important upstream regulators of gonadotropin-releasing hormone (GnRH) neurosecretion. Homologous neurons in laboratory animals are thought to modulate episodic GnRH...
Article
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Background High protein diets promote weight loss and subsequent weight maintenance but are difficult to adhere to. The mechanisms by which protein exerts these effects remain unclear. However, the amino acids produced by protein digestion may play a role in driving protein-induced satiety.Methods We tested the effects of a range of amino acids on...
Article
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Context: The combination of peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) has been proposed as a potential treatment for diabetes and obesity. However, the combined effects of these hormones, PYY(3-36) and GLP-1(7-36 amide), on glucose homeostasis are unknown. Objective: This study sought to investigate the acute effects of PYY(3-36) and...
Article
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Background and Objectives: The gut hormones peptide YY (PYY) and glucagon-like peptide 1 (GLP-1) acutely suppress appetite. The short chain fatty acid (SCFA) receptor, free fatty acid receptor 2 (FFA2) is present on colonic enteroendocrine L cells, and a role has been suggested for SCFAs in appetite regulation. Here, we characterise the in vitro an...
Article
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Kisspeptin (KP)- and neurokinin B (NKB)- synthesizing neurons of the hypothalamic arcuate nucleus play a pivotal role in the regulation of pulsatile gonadotropin-releasing hormone (GnRH) secretion. Unlike in rodents and sheep, the homologous KP and NKB neurons in the human infundibular region rarely express dynorphin- but often exhibit Substance P...
Article
Full-text available
Patients with mutations that inactivate kisspeptin signaling are infertile. Kisspeptin-54, the major circulating isoform of kisspeptin in humans, potently stimulates reproductive hormone secretion in humans. Animal studies suggest that kisspeptin is involved in generation of the luteinizing hormone surge, which is required for ovulation; therefore,...
Article
Full-text available
Obesity is a growing epidemic and current medical therapies have proven inadequate. Endogenous satiety hormones provide an attractive target for the development of drugs that aim to cause effective weight loss with minimal side-effects. Both glucagon and glucagon-like peptide 1 (GLP-1) reduce appetite and cause weight loss. Additionally, glucagon i...
Article
Background The peptide hormone kisspeptin is essential for human reproduction, acting on the hypothalamus to stimulate gonadotrophin releasing hormone (GnRH) secretion. Kisspeptin is currently being evaluated as a novel therapeutic for women with infertility. However some animal studies suggest that kisspeptin may also stimulate growth hormone (GH)...
Article
Full-text available
Ghrelin, which is a stomach-derived hormone, increases with fasting and energy restriction and may influence eating behaviors through brain hedonic reward-cognitive systems. Therefore, changes in plasma ghrelin might mediate counter-regulatory responses to a negative energy balance through changes in food hedonics. We investigated whether ghrelin a...
Article
Background: Kisspeptin is an RF amide peptide hormone critical for reproductive function. Kisspeptin is also abundantly expressed in the placenta, where it has an important physiological role in regulating placental invasion. Accordingly, plasma kisspeptin levels rise dramatically during normal pregnancy. Lower plasma levels of kisspeptin are assoc...
Article
Background: Women with hypothalamic amenorrhoea (HA) have reduced LH pulsatility causing amenorrhea and infertility. Estrogen supplementation provides symptomatic relief for women with HA, but does not restore the pulsatile pattern of LH secretion which necessary for fertility. Kisspeptin-54 is a recently identified hormone, which potently stimulat...
Article
Background: Peptide-YY is synthesised and secreted by specialised cells in the ileum and colon. Levels increase following food intake, having a satiety effect. Baseline and postprandial levels of PYY were found to be lower in obese subjects compared to lean, negatively correlating with the subjects BMI, however obese subjects were sensitive to the...
Article
Background: In vitro fertilisation (IVF) is an effective treatment for infertility, but can cause the ovarian hyper-stimulation syndrome (OHSS), which is associated with serous effusions, circulatory collapse, and even death. The use of human chorionic gonadotrophin (hCG) stimulates oocyte maturation during IVF, but is also the major cause of OHSS....
Article
A decade ago, genetic disruption of the kisspeptin signalling pathway was observed to cause hypogonadotrophic hypogonadism. Hypothalamic kisspeptin acts by stimulating secretion of endogenous GnRH. Our research has investigated the physiological effects of kisspeptin in women, with the overarching aim of determining if kisspeptin could be used to t...
Article
Background: Kisspeptin is an RF amide peptide hormone critical for reproductive function. Kisspeptin is also abundantly expressed in the placenta, where it has an important physiological role in regulating placental invasion. Accordingly, plasma kisspeptin levels rise dramatically during normal pregnancy. Lower plasma levels of kisspeptin are assoc...
Article
Full-text available
Background: The peptide hormone kisspeptin is essential for human reproduction, acting on the hypothalamus to stimulate GnRH secretion. Kisspeptin is emerging as a possible novel therapeutic for women with infertility. However animal studies suggest that kisspeptin may also stimulate pituitary secretion of GH, prolactin, and TSH, which has importan...
Article
Background: IVF is an effective treatment for infertility, but can cause the ovarian hyper-stimulation syndrome (OHSS), which is associated with serous effusions, cardiac tamponade, circulatory collapse, and even death. Injection of human chorionic gonadotrophin (hCG) stimulates oocyte maturation during IVF, but is also the major cause of OHSS. The...
Article
Full-text available
Relaxin-3 is a member of the insulin superfamily. It is expressed in the nucleus incertus of the brainstem which has projections to the hypothalamus. Relaxin-3 binds with high affinity to RXFP1 and RXFP3. RXFP3 is expressed within the hypothalamic paraventricular nucleus (PVN), an area central to the stress response. The physiological function of r...
Article
Full-text available
Hypothalamic amenorrhea (HA) is the one of the most common causes of period loss in women of reproductive age, and is associated with deficient LH pulsatility. High dose kisspeptin-54 acutely stimulates LH secretion in women with HA, but chronic administration causes desensitisation. GnRH has paradoxical effects on reproductive activity; we therefo...
Article
Kisspeptin (encoded by the KISS1 gene) is a crucial regulator of normal reproductive function. In human beings, KISS1 deletion results in a failure to go through puberty whereas activating mutations result in central precocious puberty. Administration of kisspeptin induces ovulation in rodents and sheep, but whether exogenous kisspeptin can alter t...
Article
Although in-vitro fertilisation (IVF) treatment allows infertile couples to conceive, it can result in a potentially life-threatening condition termed the ovarian hyperstimulation syndrome (OHSS). The major cause of OHSS is use of human chorionic gonadotropin (hCG) in current IVF protocols for initiating oocyte maturation. The development of a more...
Article
Neuromedin B (NMB) is a highly conserved bombesin-related peptide found in mammals. NMB mRNA is detected in the central nervous system (CNS) and is highly expressed in the rat hypothalamus, in particular the medial preoptic area and the arcuate nucleus. The mammalian bombesin family of receptors consists of three closely related G protein coupled r...
Article
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Background: Neurokinin B (NKB) is a member of the tachykinin family of peptides. Inactivating mutations in the tachykinin 3 or tachykinin 3 receptor gene are associated with pubertal failure and congenital hypogonadotrophic hypogonadism in humans. This suggests that NKB may have a critical role in human reproduction. The effects of NKB administrat...
Article
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Roux-en-Y gastric bypass (RYGB) has greater efficacy for weight loss in obese patients than gastric banding (BAND) surgery. We hypothesise that this may result from different effects on food hedonics via physiological changes secondary to distinct gut anatomy manipulations. We used functional MRI, eating behaviour and hormonal phenotyping to compar...
Article
Full-text available
Neurons synthesizing neurokinin B (NKB) and kisspeptin (KP) in the hypothalamic arcuate nucleus represent important upstream regulators of pulsatile gonadotropin-releasing hormone (GnRH) neurosecretion. In search of neuropeptides co-expressed in analogous neurons of the human infundibular nucleus (Inf), we have carried out immunohistochemical studi...
Article
Meals high in protein induce greater intermeal satiety than meals high in fat and carbohydrates. We studied the gut hormone response and subsequent food intake after breakfasts high in protein, carbohydrate or high in fat controlled for volume, calories and appearance. Eight healthy volunteers participated in this randomized three-way crossover stu...
Article
Kisspeptin is a hypothalamic neuropeptide playing a physiological role in human reproduction. Genetic over-activation of kisspeptin causes precocious puberty in children. Concentrations of circulating kisspeptin are low in adults. The concentrations of plasma kisspeptin in boys and girls have not been studied previously. Blood was obtained from 51...
Article
Congenital leptin deficiency, a rare genetic disorder due to a homozygous mutation in the leptin gene (LEP), is accompanied by extreme obesity and hyperphagia. A number of gastrointestinal hormones have been shown to critically regulate food intake but their physiological role in hyperphagic response in congenital leptin deficiency has not been elu...
Article
Full-text available
Study question What is the conservative estimate of age-specific cumulative live birth rates following minimal ovarian stimulation/natural cycle IVF in unselected infertile patients?
Article
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This abstract is under a press embargo
Article
Prevention of weight gain in adults is a major public health target. Animal experiments have consistently demonstrated a relationship between fermentable carbohydrate intake, such as oligofructose, anorectic gut hormones, and appetite suppression and body weight control. This study was designed to determine the dose of oligofructose which would aug...
Article
Background: The KISS1 gene, is a critical regulator of normal reproductive function. In humans, KISS1 deletion results in a failure to go through puberty while activating mutations result in central precocious puberty. Administration of kisspeptin induces ovulation in rodents and sheep. However chronic exposure to exogenous kisspeptin-54 leads to p...
Article
Full-text available
Introduction: Kisspeptin-54 is a recently identified hormone, which potently stimulates GnRH secretion within the hypothalamus. Women with hypothalamic amenorrhoea (HA, hypogonadotrophic hypogonadism associated with low body weight) have reduced LH pulsatility causing amenorrhea and infertility. We have previously demonstrated that exogenous admini...
Article
Obesity is a growing global epidemic and current medical therapies have proven inadequate. Endogenous satiety hormones provide an attractive target for the development of drugs which aim to cause effective weight loss with minimal side effects. Two related peptide hormones, glucagon and glucagon-like peptide 1 (GLP-1), are the subject of this inves...
Article
Full-text available
Background: Glucagon and glucagon-like peptide-1 (GLP-1) are evolutionarily related anorectic hormones. Glucagon also increases energy expenditure. The combination of glucagon and GLP-1 could cause weight loss through a simultaneous reduction in food intake and increased energy expenditure. However, the effect of combined administration of glucago...
Article
Full-text available
Glucagon and glucagon-like peptide (GLP)-1 are the primary products of proglucagon processing from the pancreas and gut, respectively. Giving dual agonists with glucagon and GLP-1 activity to diabetic, obese mice causes enhanced weight loss and improves glucose tolerance by reduction of food intake and by increase in energy expenditure (EE). We aim...
Article
Pancreatic polypeptide (PP), peptide YY (PYY) and neuropeptide Y (NPY), members of the PP-fold family share a high degree of sequence homology. Nuclear Magnetic Resonance (NMR) and X-ray crystallography studies have shown these peptides can adopt a tightly organized tertiary structure called the PP-fold, which has long been assumed to be the active...
Article
Peptidergic neurons synthesizing kisspeptin (KP) and neurokinin B (NKB) in the hypothalamic infundibular nucleus have been implicated in negative sex steroid feedback to GnRH neurons. In laboratory rodents, testosterone decreases KP and NKB expression in this region. In the present study, we addressed the hypothesis that the weakening of this inhib...
Article
Background and purpose: Prokineticin 2 (PK2) has recently been shown to acutely reduce food intake in rodents. We aimed to determine the CNS sites and receptors that mediate the anorectic effects of peripherally administered PK2 and its chronic effects on glucose and energy homeostasis. Experimental approach: We investigated neuronal activation...
Article
Previous immunohistochemical and in situ hybridization studies of sheep, goats, and rodents indicated that kisspeptin (KP), neurokinin B (NKB), and dynorphin A (DYN) are extensively colocalized in the hypothalamic arcuate nucleus, thus providing a basis for the KP/NKB/DYN (KNDy) neuron concept; in both sexes, KNDy neuropeptides have been implicated...
Article
Full-text available
Gastric bypass leads to the remission of type 2 diabetes independently of weight loss. Our hypothesis is that changes in bile flow due to the altered anatomy may partly explain the metabolic outcomes of the operation. We prospectively studied 12 patients undergoing gastric bypass and six patients undergoing gastric banding over a 6-wk period. Plasm...
Article
In the pancreas, peptide YY (PYY) is expressed by a subpopulation of nonbeta cells in the islets of Langerhans. We investigated the function of these cells in the pancreas of adult mice. We generated mice in which administration of diphtheria toxin (DT) led to specific ablation of PYY-expressing cells. We investigated the effects of loss of PYY cel...
Article
The aim of this study was to prospectively evaluate plasma kisspeptin levels in 129 singleton pregnancies with diabetes [pregestational insulin-dependent diabetes mellitus (type 1) and gestational diabetes (GD)] and hypertensive disease [chronic hypertension (CH), gestational hypertension, and preeclampsia (PE)] as a potential marker of placental d...
Article
Full-text available
To the Editor: More than 15 000 women in the US die from ovarian carcinoma annually (1). The most important determinant of survival in ovarian carcinoma cases is tumor stage. Most patients presenting with disease confined to the ovaries (stage 1) can be cured, with a 5-year survival rate of >90% (1). Spread of the tumor outside the ovaries (stages...
Article
Background:Patients show an elevated postprandial satiety gut hormone release after Roux-en-Y Gastric bypass (gastric bypass). The altered gut hormone response appears to have a prominent role in the reduction of appetite and body weight (BW) after gastric bypass. Patients with insufficient BW loss after gastric bypass have an attenuated postprandi...
Article
Full-text available
The secretory output of gonadotropin-releasing hormone (GnRH) neurons is critically influenced by peptidergic neurons synthesizing kisspeptins (KP) and neurokinin B (NKB) in the hypothalamic infundibular nucleus (Inf). These cells mediate negative feedback effects of sex steroids on the reproductive axis. While negative feedback is lost in postmeno...
Article
Kisspeptin peptides are critical in human reproductive physiology and are potential therapies for infertility. Kisspeptin-10 stimulates gonadotropin release in both male and female rodents. However, few studies have investigated the effects of kisspeptin-10 on gonadotropin release in humans, and none have investigated the effect in women. If kisspe...
Data
Imaging measures (cluster peaks meeting a criterion of p < 0.05, z > 1.6) for saline infusion (in the fed and fasted state) are shown. The response of each of the a priori ROIs to the picture processing task for saline infusion (in the fed and fasted state) is highlighted in bold in the second half of the table.
Article
Full-text available
Obesity is a major public health issue worldwide. Understanding how the brain controls appetite offers promising inroads toward new therapies for obesity. Peptide YY (PYY) and glucagon-like peptide 1 (GLP-1) are coreleased postprandially and reduce appetite and inhibit food intake when administered to humans. However, the effects of GLP-1 and the w...
Article
Full-text available
Understanding the etiologic mechanisms underlying impaired glucose tolerance in obstructive sleep apnea (OSA) would assist development of therapies against this comorbidity. We hypothesized that in patients with OSA impaired glucose tolerance (IGT) would be associated with elevated levels of hormones associated with appetite regulation (leptin, ghr...
Article
Peptide YY(3-36) (PYY(3-36)) is a gut hormone that acts on Y2 receptors to reduce appetite. Obese humans are sensitive to the anorectic effects of PYY(3-36) and display a blunted postprandial rise in PYY(3-36). Bariatric surgery results in increased circulating PYY-immunoreactivity, which appears to play a role in postoperative weight loss. The uti...
Article
The objectives of this phase 1 study were to confirm the tolerability of single ascending subcutaneous doses of PP 1420 in healthy subjects, to assess its adverse effects and to investigate the drug's pharmacokinetics and dose proportionality. This was a double-blind, placebo-controlled, randomized study. There were three dosing periods. Each subje...
Article
Roux-en-Y gastric bypass (gastric bypass) patients reportedly have changes in perception and consumption of sweet-tasting foods. This study aimed to further investigate alterations in sweet food intake in rats and sucrose detection in humans after gastric bypass. Wistar rats were randomized to gastric bypass or sham-operations and preference for su...
Article
Vasoactive intestinal peptide (VIP) is a 28 amino acid peptide expressed throughout the peripheral and central nervous systems. VIP and the VIP receptor VPAC(2)R are expressed in hypothalamic nuclei involved in the regulation of energy homeostasis. VIP has been shown to be involved in the regulation of energy balance in a number of non-mammalian ve...
Article
Full-text available
Endocannabinoid antagonism as a treatment for obesity and the metabolic syndrome became a hugely anticipated area of pharmacology at the start of the century. The CB1 receptor antagonist Rimonabant entered the European mass market on the back of several trials showing weight loss benefits alongside improvements in numerous other elements of the met...