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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nutritional status influences hormone secretion from specialized enteroendocrine cells within the gut mucosa. These hormones regulate food intake by mediating information to central neurocircuitries in the brainstem and forebrain (eg, hypothalamic nuclei). Intestinal enteroendocrine cells were believed to be the main source of gut peptides regulating food intake. However, recent evidence highlights a specific endocrine cell within the oxyntic glands of the stomach as an important player in appetite control. Acylated ghrelin is the only known orexigenic hormone peripherally produced in gastric X/A-like cells and centrally acting to stimulate food intake. Recent advances led to the assumption that des-acylated ghrelin, coreleased with acylated ghrelin, is also involved in regulating food intake. This, and the novel observation that nesfatin-1, which inhibits food intake, is expressed in ghrelin-producing cells of the stomach, supports an important role for gastric X/A-like cells in regulating food intake. Another peptide, obestatin, was initially described as a ghrelin gene product inhibiting food intake, but subsequent studies produced controversial data and its action as an anorexic factor is doubtful. Importantly, synergistic interactions between ghrelin and intestinal peptides seem to orchestrate food intake and body weight regulation, which may have implications for understanding mechanisms leading to the treatment of obesity.
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PMID:Regulation of food intake: the gastric X/A-like endocrine cell in the spotlight. 1990 20

Obestatin is a recently discovered gastrointestinal hormone. It might play a role in the pathophysiology of obesity. We tried to investigate the expression of obestatin in gastric body mucosa in overweight (BMI>or=24 kg/m(2))/obese (BMI>or=28 kg/m(2)) patients. Thirty overweight/obese patients and 20 healthy controls were included in the study. Biopsy specimens of gastric mucosa were obtained from the middle body of the greater curvature. Obestatin expression in gastric mucosa was evaluated by immunohistochemistry. Fasting plasma obestatin levels were measured by radioimmunoassay. The number of obestatin-positive cells in gastric body mucosa was significantly lower in overweight and obese patients than that in healthy subjects. The plasma concentrations of obestatin were also decreased in overweight and obese patients. There was a positive correlation between the numbers of obestatin-positive cells in the gastric body mucosa and circulating obestatin levels. The results indicate that overweight and obese subjects have a reduction in the number of obestatin-positive cells in gastric body mucosa.
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PMID:Decreased gastric body mucosa obestatin expression in overweight and obese patients. 1991 22

Eating disorders, obesity and cachexia endanger the lives of millions of people worldwide. Fortunately, in last decade, there has been a rapid and substantial progress toward uncovering the molecular and neural mechanisms by which energy imbalance develops. In 1999, ghrelin was identified as the first orexigenic gut-derived peptide. It stimulates appetite and controls the gastric motility and the acid secretion through the activation of the growth hormone secretagogue-receptor. After the discovery of ghrelin, other forms of ghrelin-related proteins were isolated from the rat stomach. The unmodified des-n-octanoyl form (des-acyl ghrelin) and the recent obestatin act through distinct receptors and contrarily to acyl ghrelin, show an anorexigenic activity. The finding that these three peptide hormones derive from the same precursor exert opposing physiological actions, highlights the importance of post-translational regulatory mechanisms. Further investigations are required to highlight the complexity of ghrelin physiology in order to better understand the mechanisms regulating the energy balance and provide a successful treatment of eating disorders, obesity and cachexia.
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PMID:Appetite and gastrointestinal motility: role of ghrelin-family peptides. 1994 99

A breakthrough using "reverse pharmacology" identified and characterized acyl ghrelin from the stomach as the endogenous cognate ligand for the growth hormone (GH) secretagogue receptor (GHS-R) 1a. The unique post-translational modification of O-n-octanoylation at serine 3 is the first in peptide discovery history and is essential for GH-releasing ability. Des-acyl ghrelin, lacking O-n-octanoylation at serine 3, is also produced in the stomach and remains the major molecular form secreted into the circulation. The third ghrelin gene product, obestatin, a novel 23-amino acid peptide identified from rat stomach, was found by comparative genomic analysis. Three ghrelin gene products actively participate in modulating appetite, adipogenesis, gut motility, glucose metabolism, cell proliferation, immune, sleep, memory, anxiety, cognition, and stress. Knockdown or knockout of acyl ghrelin and/or GHS-R1a, and overexpression of des-acyl ghrelin show benefits in the therapy of obesity and metabolic syndrome. By contrast, agonism of acyl ghrelin and/or GHS-R1a could combat human anorexia-cachexia, including anorexia nervosa, chronic heart failure, chronic obstructive pulmonary disease, liver cirrhosis, chronic kidney disease, burn, and postsurgery recovery, as well as restore gut dysmotility, such as diabetic or neurogenic gastroparesis, and postoperative ileus. The ghrelin acyl-modifying enzyme, ghrelin O-Acyltransferase (GOAT), which attaches octanoate to serine-3 of ghrelin, has been identified and characterized also from the stomach. To date, ghrelin is the only protein to be octanylated, and inhibition of GOAT may have effects only on the stomach and is unlikely to affect the synthesis of other proteins. GOAT may provide a critical molecular target in developing novel therapeutics for obesity and type 2 diabetes.
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PMID:Ghrelin gene products and the regulation of food intake and gut motility. 2003 70

Data accumulated over recent years have significantly advanced our understanding of growth factors, cytokines, and hormones in breast milk. Here we deal with leptin, adiponectin, IGF-I, ghrelin, and the more recently discovered hormones, obestatin, and resistin, which are present in breast milk and involved in food intake regulation and energy balance. Little is known about these compounds in infant milk formulas. Nutrition in infancy has been implicated in the long-term tendency to obesity, and a longer duration of breastfeeding appears to protect against its development. Diet-related differences in serum leptin and ghrelin values in infancy might explain anthropometric differences and differences in dietary habits between breast-fed and formula-fed infants also later in life. However, there are still gaps in our understanding of how hormones present in breast milk affect children. Here we examine the data related to hormones contained in mother's milk and their potential protective effect on subsequent obesity.
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PMID:Breast milk hormones and their protective effect on obesity. 2004 53

The aims of this study are to examine in children: (i) obesity-related alterations in satiety factors such as leptin, ghrelin, and obestatin; (ii) the link between satiety factors and cardiometabolic risk factors; and (iii) the impact of a physical activity-based lifestyle intervention on the levels of these satiety factors in the obese. We studied a total of 21 adolescents (BMI percentile, 99.0 +/- 0.6 for 15 obese and 56.2 +/- 1.1 for 6 lean). The obese subjects underwent a 3-month randomized controlled physical activity-based lifestyle intervention. Leptin, soluble leptin receptor (sOB-R), ghrelin, and obestatin levels were determined as the primary outcome measures. Other markers of cardiometabolic disease such as inflammation and insulin resistance were also determined. Body composition was measured by dual-energy X-ray absorptiometry. The concentrations of ghrelin, obestatin, and sOB-R were significantly lower in the obese children compared to the lean controls, whereas that of leptin was higher (all P < 0.05). Although intervention led to a net increase in obestatin (P < 0.01) and no change in ghrelin levels, the balance between ghrelin and obestatin (ratio of ghrelin to obestatin, G/O) decreased (P < 0.02). Intervention reduced leptin and increased sOB-R (P < 0.01 for both). Significant associations between satiety factors and other cardiometabolic risk factors were also observed. Taken together, alterations in the levels of satiety factors are evident early in the clinical course of obesity, but physical activity-based lifestyle intervention either prevented their continued increase or normalized their levels. These beneficial effects appear to aid in the maintenance of body weight and reduction in cardiovascular risk.
Obesity (Silver Spring) 2010 Sep
PMID:Changes in circulating satiety hormones in obese children: a randomized controlled physical activity-based intervention study. 2009 40

Ghrelin is a 28 amino acid peptide hormone derived from the 117 amino acid proghrelin, following cleavage by proprotein convertase 1 (PC1). In this study, we comprehensively assessed the tissue distribution and the effect of fasting and obesity on preproghrelin, Exon-4D, PC1 and GOAT expression and proghrelin-derived peptide (PGDP) secretion. The stomach was the major source of preproghrelin expression and PDGPs, followed by the small intestine. The remaining peripheral tissues (including the brain and pancreas) contained negligible expression levels. We detected obestatin in all stomach proghrelin cells, however, 22% of proghrelin cells in the small intestine did not express obestatin. There were strain differences in ghrelin secretion in response to fasting between CD1 and C57BL/6 mice. After a 24 hour-fast, CD1 mice had increased plasma levels of total ghrelin and obestatin with no change in preproghrelin mRNA or PGDP tissues levels. C57BL/6 mice showed a different response to a 24 hour-fast having increased proghrelin mRNA expression, stomach acylated ghrelin peptide and no change in plasma obestatin in C57BL/6 mice. In obese mice (ob/ob and diet-induced obesity (DIO)) there was a significant increase in preproghrelin mRNA levels while tissue and plasma PGDP levels were significantly reduced. Fasting did not affect PGDP in obese mice. Obese models displayed differences in GOAT expression, which was elevated in DIO mice, but reduced in ob/ob mice. We did not find co-localization of the leptin receptor in ghrelin expressing stomach cells, ruling out a direct effect of leptin on stomach ghrelin synthesis and secretion.
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PMID:Tissue distribution and effects of fasting and obesity on the ghrelin axis in mice. 2036 13

Weight loss treatments include diets, drugs, physical training, and surgery, namely bariatric or obesity surgery. The current standard for bariatric surgery is gastric bypass. There are common beliefs that gastric bypass induces body weight loss because of a reduced food intake and that high-fat diet induces overweight and obesity because of overnutrition. The principal aim of the studies on rats summarized herein was to better understand the physiological mechanisms by which gastric bypass achieves body weight loss and by which high-fat diet induces obesity. The results indicated that gastric bypass efficiently reduced body weight, particularly the fat compartment, which was unlikely to be caused by early satiety, reduced food intake or malabsorption, and that large meal size, but not overnutrition, was mainly responsible for high-fat diet-induced obesity. It was unclear whether gastric ghrelin, obestatin and/or amine in the A-like cells were involved in this context.
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PMID:Feeding behavior and body weight development: lessons from rats subjected to gastric bypass surgery or high-fat diet. 2038 43

Ghrelin and obestatin are two gastrointestinal peptides obtained by post-translational processing of a common precursor, preproghrelin. Ghrelin is an orexigenic and adipogenic peptide and a potent growth hormone secretagogue (GHS) modified by the enzyme ghrelin-O-acyl-transferase to bind and activate its receptor, the GHS-R. The ghrelin/GHS-R pathway is complex and the effects of ghrelin on GH secretion, adiposity and food intake appear to be relayed by distinct mechanisms involving different transduction signals and constitutive activity for the GH-R, different cofactors as modulators of endogenous ghrelin signalling and/or alternative ghrelin receptors. The discovery of obestatin in 2005 brought an additional level of complexity to this fascinating system. Obestatin was initially identified as an anorexigenic peptide and as the cognate ligand for GPR39, but its effect on food intake and its ability to activate GPR39 are still controversial. Although several teams failed to reproduce the anorexigenic actions of obestatin, this peptide has been shown to antagonise GH secretion and food intake induced by ghrelin and could be an interesting pharmacological tool to counteract the actions of ghrelin. Ghrelin and obestatin immunoreactivities are recovered in the blood with an ultradian pulsatility and their concentrations in plasma vary with the nutritional status of the body. It is still a matter of debate whether both hormones are regulated by independent mechanisms and whether obestatin is a physiologically relevant peptide. Nevertheless, a significant number of studies show that the ghrelin/obestatin ratio is modified in anorexia nervosa and obesity. This suggests that the ghrelin/obestatin balance could be essential to adapt the body's response to nutritional challenges. Although measuring ghrelin and obestatin in plasma is challenging because many forms of the peptides circulate, more sensitive and selective assays to detect the different preproghrelin-derived peptides are being developed and may be the key to obtaining a better understanding of their roles in different physiological and pathological conditions.
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PMID:The ghrelin/obestatin balance in the physiological and pathological control of growth hormone secretion, body composition and food intake. 2045 3

Gut hormones play key roles in the regulation of energy homeostasis. However, little is known about the long- and short-term effects of changing dietary fat content on gut hormones. We aim to examine the effects of changing dietary fat content on plasma gut hormone concentrations in diet-induced obese (DIO) and diet-resistant (DR) rats. After inducing obesity with a high-fat (HF) diet, male Sprague-Dawley rats were divided into three groups according to their body-weight gain: DIO; DR; control (CON). The DIO and DR rats were further divided in random into two groups. One continued on a HF diet and the other switched to a low-fat (LF) diet for an additional 4 weeks. Finally, each group was randomly divided into three subgroups (n 8): fasted; fasted-refed HF; fasted-refed LF diet groups. Replacing a HF diet with a LF diet for 4 weeks resulted in less fat mass, higher fasting and post-HF plasma ghrelin concentration and lower postprandial plasma cholecystokinin concentration in the DIO and DR rats. Acute switching dietary fat resulted in significantly higher post-HF plasma ghrelin concentrations than post-LF ghrelin concentrations in the DR rats on LF diet (DRLF) and DIO rats on LF diet (DIOLF) rats, and significantly higher post-HF obestatin concentrations than post-LF obestatin concentrations in the CON, DR rats on HF diet (DRHF) and DRLF rats. Dietary fat content appears to play a role in the gut hormone profile, which may consequently influence fat mass.
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PMID:Effects of changing dietary fat content on plasma gut hormone concentrations in diet-induced obese and diet-resistant rats. 2105 80


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