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

Since adipose tissue was shown to be more than a storage organ, the many cytokines it produces have been identified, along with their roles in energy homeostasis, appetite, and insulin resistance. Concurrently, numerous gut hormones with a diversity of effects have been discovered. They include, amongst many others, peptide YY, ghrelin and oxyntomodulin. As these peptides have been investigated, the potential for their use as novel anti-obesity and antidiabetic therapies has been realized. In this chapter we describe the actions of four of the peptides that have been proposed as the basis for promising new therapies for diabetes: leptin, adiponectin, obestatin and peptide YY. They each have an effect on appetite and, directly or indirectly, on glucose metabolism. We synthesize available data for these peptides and consider the therapeutic potential of each.
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PMID:Potential therapies based on antidiabetic peptides. 1805 40

Obestatin, shown to reduce feed intake and gain in body weight in rodents, is a very attractive candidate to be used against obesity. In this study, we aimed to investigate the relationship between the primary structure and activity of obestatin. Also of interest to us is a peptide of minimal length that closely mimics obestatin. Towards the same, we synthesized rodent obestatin and three overlapping fragments spanning residues 1-13, 6-18, and 11-23 of obestatin. These peptides subsequent to purification and characterization were tested upon adult male mice for their ability to reduce feed intake and gain in body weight. The N-terminal peptide (residues 1-13) mimicked obestatin the closest. The middle fragment (residues 6-18) significantly reduced epididymal fat without much altering feed intake or body weight.
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PMID:Fragments of obestatin as modulators of feed intake, circulating lipids, and stored fat. 1808 29

Ghrelin, a gastric peptide hormone, has been reported to regulate GH secretion and energy homeostasis. Here, we examined the effect of des-acyl ghrelin driven from the fatty acid-binding protein-4 (FABP4) promoter on adiposity and glucose metabolism. A high level of expression of des-acyl ghrelin (692 +/- 293 fmol/g fat) in adipose tissue was detected in FABP4-ghrelin transgenic mice, but not in wild-type littermates. Circulating des-acyl ghrelin was significantly higher in FABP4-ghrelin transgenic mice (8409 +/- 3390 pm) compared with wild-type mice (513 +/- 58 pm). No significant change was observed for plasma acylated ghrelin and obestatin. Epididymal and perirenal fat masses decreased 35 +/- 9 and 52 +/- 9%, respectively, in FABP4-ghrelin transgenic mice. FABP4-ghrelin transgenic mice are resistant to obesity induced by high-fat diet. Brown fat mass was not affected by overexpression of ghrelin in adipose tissue. Glucose tolerance tests showed glucose levels to be significantly lower in FABP4-ghrelin transgenic mice than in controls after glucose administration. Insulin sensitivity testing showed that FABP4-ghrelin transgenic mice had a 28 +/- 5% greater hypoglycemic response to insulin. Our study demonstrates that overexpression of ghrelin from the FABP4 promoter impairs the development of white adipose tissues, and alters glucose tolerance and insulin sensitivity in mice.
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PMID:Effect of des-acyl ghrelin on adiposity and glucose metabolism. 1853 5

Ghrelin, a 28-amino acid peptide, was recently identified from the stomach as the first endogenous ligand for growth hormone secretagogue receptors (previously known as orphan receptors). Ghrelin was discovered by 'reverse pharmacology'. The acyl ghrelin peptide features a unique post-translational modification of O-n-octanoylation at serine 3, and is the only gastrointestinal signal that increases meal size. However, des-acyl ghrelin accounts for the major forms in the plasma. Most recently, obestatin, a novel 23-amino acid peptide, was derived from the mammalian preproghrelin gene, which also encodes ghrelin, by a bioinformatic approach. This at-the-cutting-edge review focuses on three ghrelin gene products: acyl ghrelin, des-acyl ghrelin, and the newly identified obestatin. Their updated orexigenic and anorexigenic effects on food intake, their signal transduction pathways from the periphery to the brain, as well as their roles in modulating gastrointestinal motility, and potential applications in the many fields of medicine such as eating disorders, obesity/anorexia-cachexia, and gastrointestinal dysmotility under different conditions, are critically addressed.
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PMID:At the cutting edge: ghrelin gene products in food intake and gut motility. 1893 75

The high prevalence of obesity and diabetes will lead to higher rates of morbidity and mortality. It is well known that ghrelin plays a potential role in obesity and diabetes. Obestatin, a novel 23 amino acid amidated peptide encoded by the same gene that encodes ghrelin, was initially reported to have opposite actions to ghrelin in the regulation of food intake, emptying of the stomach and body weight. Recent work suggests that obestatin also regulate beta-cell survival and insulin secretion. The ghrelin-obestatin system is, therefore, a promising target for the developing of new drugs for the treatment of obesity and diabetes. This review summarizes the interrelationship between obestatin, obesity and diabetes.
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PMID:Obestatin, obesity and diabetes. 1899 81

Obestatin, derived from the same gene as the hunger hormone ghrelin, may reduce food intake in animals. The role of obestatin in human physiology is unclear. We evaluated cross-sectional associations between participant characteristics and fasting levels of obestatin as well two other hormones associated with energy balance, ghrelin and leptin. Data are from the baseline visit of the Optimal Macronutrient Intake Trial to Prevent Heart Disease (OMNI-Heart) Trial that enrolled adults with elevated blood pressure (systolic 120-159 mm Hg or a diastolic of 80-99 mm Hg) but who were otherwise healthy. Partial Spearman's correlations and linear regression models estimated the association between age, gender, BMI, physical activity, and smoking with fasting hormones. Obestatin was directly associated with ghrelin (r = 0.45, P < 0.05). On average, overweight (BMI 25-30) and obese (BMI > 30) individuals had obestatin concentrations that were 12.6 (s.d. 8.8) and 25.4 (s.d. 8.4) pg/ml lower compared to normal weight (BMI < 25) individuals, respectively (P for trend = 0.002). Overweight (BMI 25-30) and obese (BMI > 30) individuals had ghrelin concentrations that were 161.7 (s.d. 69.6) and 284.7 (s.d. 66.5) pg/ml lower compared to normal weight (BMI < 25) individuals, respectively (P for trend <0.0001). A 5 unit increase in BMI was associated with 41.3% (s.d. 4.3%) (P < 0.0001) higher leptin. Obestatin and ghrelin are directly correlated and share the same patterns of association with participant characteristics. Modifiable risk factors for chronic diseases, such as BMI, are associated with fasting levels of leptin, obestatin, and ghrelin.
Obesity (Silver Spring) 2009 Feb
PMID:Characteristics associated with fasting appetite hormones (obestatin, ghrelin, and leptin). 1905 26

Ghrelin is a gut-brain peptide that has somatotropic, food intake increasing and adipogenic effects. Ghrelin is involved in modulating insulin and glucose metabolism in rodents according to recent studies. In humans acylated ghrelin reduces insulin sensitivity while unacylated ghrelin has opposite effects. In general, ghrelin seems to have diabetogenic effects. Obese, in particular abdominally obese, subjects have low ghrelin levels and decreased total ghrelin levels have been associated with metabolic syndrome and Type 2 diabetes. Most of the human studies in Type 1 diabetes have reported low ghrelin levels probably as a compensatory mechanism against hyperglycaemia. The data on obestatin in the regulation of energy balance is extremely contradictory. Interestingly, ghrelin receptor antagonists may improve glucose tolerance in rats without inducing weight gain by increasing insulin secretion. Antagonism of ghrelin function to treat diabetes is thus a fascinating idea. This review concentrates on recent findings on the orexigenic peptide ghrelin and its derivatives in metabolic disorders with emphasis put on human studies.
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PMID:Ghrelin and metabolic disorders. 1927 67

Nutrition and growth during infancy are an emerging issue because of their potential link to metabolic health disorders in later life. Moreover, prolonged breast-feeding appears to be associated with a lower risk of obesity than formula feeding. Human milk is a source of various hormones and growth factors, namely adipokines (leptin and adiponectin), ghrelin, resistin and obestatin, which are involved in food intake regulation and energy balance. These compounds are either not found in commercial milk formulas or their presence is still controversial. Diet-related differences during infancy in serum levels of factors involved in energy metabolism might explain anthropometric differences and also differences in dietary habits between breast-fed (BF) and formula-fed (FF) infants later in life, and may thus have long-term health consequences. In this context, the recent finding of higher leptin levels and lower ghrelin levels in BF than in FF infants suggests that differences in hormonal values together with different protein intake could account for the differences in growth between BF and FF infants both during infancy and later in life. In this review, we examine the data related to hormones contained in mothers' milk and their potential protective effect on subsequent obesity and metabolic-related disorders.
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PMID:Can hormones contained in mothers' milk account for the beneficial effect of breast-feeding on obesity in children? 1930 80

1. Ghrelin is a multifunctional peptide hormone that affects various processes, including growth hormone and insulin release, appetite regulation, gut motility, metabolism and cancer cell proliferation. Ghrelin is produced in the stomach and in other normal and pathological cell types. It may act as an endocrine or autocrine/paracrine factor. 2. The present article reviews recent findings in the study of ghrelin and its receptor that suggest that the ghrelin gene locus may give rise to a number of functional molecules (peptides and RNA transcripts) in addition to ghrelin. 3. The ghrelin gene encodes a precursor protein, preproghrelin, from which ghrelin and other potentially active peptides are derived by alternative mRNA splicing and/or proteolytic processing. The metabolic role of the peptide obestatin, derived from the preproghrelin C-terminal region, is contentious. However, obestatin has direct effects on cell proliferation. 4. The regulation of ghrelin expression and the mechanisms through which the peptide products arise are unclear. We have recently re-examined the organization of the ghrelin gene and identified several novel exons and transcripts. One transcript, which lacks the ghrelin-coding region of preproghrelin, contains the coding sequence of obestatin. 5. Furthermore, we have identified an overlapping gene on the antisense strand of ghrelin, namely GHRLOS, which generates transcripts that may function as non-coding regulatory RNAs or code for novel, short bioactive peptides. 6. The identification of these novel ghrelin-gene related transcripts and peptides raises critical questions regarding their physiological function and their potential role in obesity, diabetes and cancer.
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PMID:Ghrelin gene-related peptides: multifunctional endocrine / autocrine modulators in health and disease. 1956 30

Emerging evidence indicates the potential involvement of ghrelin, an endogenous ligand for the growth hormone secretagogue receptor, in low-grade inflammatory diseases such as obesity and atherosclerosis. The goal of the present study was to use cell culture models to investigate the influences of ghrelin and obestatin in processes participating in atherogenesis. We studied monocyte adhesion, monocyte chemoattractant protein-1, and adhesion molecule expression on endothelial cells as well as binding of oxidized low-density lipoprotein (LDL) and acetylated LDL to macrophages. Ghrelin treatment increased adhesion of calcein-labeled THP-1 monocytes to EA.hy 926 endothelial cells. Simultaneously, ghrelin increased the expression of intercellular adhesion molecule-1 measured by quantitative reverse transcriptase polymerase chain reaction. Tumor necrosis factor-alpha stimulation together with ghrelin treatment decreased both monocyte adhesion and vascular cell adhesion molecule-1 and monocyte chemoattractant protein-1 expression and, together with obestatin treatment, decreased vascular cell adhesion molecule-1 expression. Finally, ghrelin and obestatin increased binding of oxidized LDL to thioglycollate-elicited mouse peritoneal macrophages. No changes were observed in the uptake of acetylated LDL by mouse J774.A1 macrophages after exposure to ghrelin or obestatin. In conclusion, we found 3 lines of in vitro evidence supporting proatherogenic properties of ghrelin in the early stages of the disease. However, in the presence of tumor necrosis factor-alpha stimulation, opposite effects of ghrelin were observed, suggesting that ghrelin may also have an anti-inflammatory role in the presence of increased inflammation, for example, during the more progressed phases of atherogenesis.
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PMID:Ghrelin and obestatin modulate early atherogenic processes on cells: enhancement of monocyte adhesion and oxidized low-density lipoprotein binding. 1960 5


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