Short‐Term Effects of Gastric Bypass Surgery on Circulating Ghrelin Levels

Morı́nigo, Rosa; Casamitjana, Roser; Moizé, Violeta; Lacy, Antonio M.; Delgado, Salvadora; Gomis, Ramón; Vidal, Josep

doi:10.1038/oby.2004.139

Cited by 99 publications

(72 citation statements)

References 47 publications

(96 reference statements)

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“…This was in contrast to the blunted pattern seen in the morbidly obese group. The results in our study contrast to other studies where no meal-induced changes in ghrelin levels were found in postoperative patients, 16,17,30 and another study reported a smaller magnitude of the decline in serum ghrelin levels after oral glucose tolerance test in patients after gastric bypass surgery compared with lean subjects. 18 On the other hand, one recent study reported a similar response to a test meal in lean and RYGBP groups and higher in operated patients than in BMI-matched controls.…”

Section: Discussioncontrasting

confidence: 99%

Meal suppression of circulating ghrelin is normalized in obese individuals following gastric bypass surgery

et al. 2006

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Objective: It has been proposed that the success of maintained weight loss in morbidly obese subjects following Roux-en-Y gastric bypass (RYGBP) surgery depends on inappropriately low circulating concentrations of the appetite-stimulating peptide ghrelin, being unresponsive to food intake. In this study, this hypothesis was examined. Design: Cross-sectional study with repeated blood samples in 40 subjects after 14 h of prolonged overnight fasting followed by a standardized mixed meal (770 kcal). Subjects: Twenty men and 20 women were included: 10 middle-aged morbidly obese (body mass index (BMI) 43.973.3 kg/ m 2 ), 10 middle-aged subjects who had undergone RYGBP at the Uppsala University Hospital (BMI 34.775.8 kg/m 2 ), 10 middleaged non-obese (BMI 23.572.2 kg/m 2 ) and 10 young non-obese (BMI 22.771.8 kg/m 2 ). Measurements: Ghrelin, glucose and insulin levels were analysed pre-and postprandially. Results: In the morbidly obese, ghrelin concentrations were lower in the morning than in the RYGBP group and did not change following the meal. In the RYGBP group, fasting ghrelin levels fell after meal intake and showed similar suppression as both agematched and young non-obese controls. The RYGBP surgery resulted in an increased meal-induced insulin secretion, which was related to the degree of postprandial ghrelin suppression. Conclusion: The present study demonstrates low circulating concentrations of ghrelin and blunted responses to fast and feeding in morbidly obese subjects. Marked weight reduction after RYGBP at our hospital is followed by a normalization of ghrelin secretion, illustrated by increased fasting levels compared to the preoperative obese state and regain of meal-induced ghrelin suppression.

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Section: Discussioncontrasting

confidence: 99%

Meal suppression of circulating ghrelin is normalized in obese individuals following gastric bypass surgery

et al. 2006

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“…Studies in adults demonstrated increasing ghrelin levels, 12-15 stable ghrelin concentrations [16][17][18][19] and decreasing ghrelin levels in weight reduction. 20 Reduction of overweight was achieved in most of these studies by gastric surgery.…”

Section: Discussionmentioning

confidence: 99%

“…9 In obese adults and children, leptin levels have shown to be increased, while ghrelin levels are decreased. 7,[9][10][11] There are only few studies consisting of only a small number of subjects, which analyze the changes in ghrelin levels due to reduction of overweight in a time period of weeks up to months with contradictory results: four studies reported increasing ghrelin levels, [12][13][14][15] four studies no changes of ghrelin levels [16][17][18][19] and one study decreasing ghrelin levels after weight reduction. 20 Until now, there is only one study on ghrelin levels in obese children after weight reduction.…”

Section: Introductionmentioning

confidence: 99%

Ghrelin levels before and after reduction of overweight due to a low-fat high-carbohydrate diet in obese children and adolescents

et al. 2005

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BACKGROUND: There are conflicting results for ghrelin changes in reduction of overweight. Increasing ghrelin levels in weight reduction are considered to be responsible for compensatory mechanisms that make the reduction of overweight unlikely to be sustained. METHODS:We have analyzed fasting serum ghrelin levels, weighed dietary record and, as biochemical markers of clinically relevant reduction of overweight, leptin, adiponectin and insulin levels and insulin resistance measured by homeostasis model assessment (HOMA) at baseline and after a 1-y outpatient weight reduction program based on a high-carbohydrate and low-fat diet in 37 obese children (median age 10 y). We divided these children into two subgroups according to their degree of weight loss (substantial reduction of overweight: decrease in SDS-BMIZ0.5). Furthermore, we analyzed ghrelin levels in 16 normalweight children. RESULTS: Obese children demonstrated significant (Po0.001) lower ghrelin levels compared to normal-weight children. Daily caloric intake (P ¼ 0.004) and percentage fat content decreased significantly (Po0.001), while percentage carbohydrate content increased significantly (P ¼ 0.003) between baseline and 1-y follow-up in the obese children. The substantial reduction of overweight in 16 children (median SDS-BMI ¼ À0.7) was associated with significant changes in insulin resistance (median decrease of HOMA 27%; P ¼ 0.013), insulin (median decrease 25%, P ¼ 0.036), adiponectin (median increase 15%; P ¼ 0.003), and leptin levels (median decrease 19%; P ¼ 0.023), while there were no significant changes in ghrelin levels (median increase 4%; P ¼ 0.326). In the 21 children without substantial reduction of overweight (median SDS-BMI ¼ À0.3), there were no significant changes in insulin resistance and in insulin, adiponectin, leptin and ghrelin levels. CONCLUSIONS: We conclude that in obese children, low-fat high-carbohydrate diet-induced weight loss does not change ghrelin secretion, but significantly decreases leptin levels, increases adiponectin levels and improves insulin resistance determined by significantly decreased insulin resistance indices as well as lowered serum insulin levels.

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“…Much is known regarding life with chronically reduced ghrelin levels because thousands of individuals have undergone Rouxen-Y gastric bypass surgery, which reduces ghrelin levels by 50-70% for weeks relative to weight-loss controls. Postsurgical ghrelin levels are even lower after total gastrectomy or sleeve gastrectomy (removal of the fundus) and remain so in the long-term (34)(35)(36)(37)(38)(67)(68)(69)(70)(71)(72)(73)(74)(75)(76)(77). The Roux-en-Y gastric bypass and sleeve gastrectomy surgeries both produce massive weight reduction, greater than those of other surgical procedures that less effectively reduce ghrelin levels and improve the health of previously morbidly obese patients with low complication rates (37,78,79).…”

Section: Resultsmentioning

confidence: 99%

Catalytic antibody degradation of ghrelin increases whole-body metabolic rate and reduces refeeding in fasting mice

Mayorov

Amara

Chang

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Obesity is a chronic, costly, and globally prevalent condition, with excess caloric intake a suspected etiologic factor. Nonsurgical treatments are modestly efficacious, and weight loss maintenance is hampered by anti-famine homeostatic mechanisms. Ghrelin, a gastric hormone linked to meal initiation, energy expenditure, and fuel partitioning, is hypothesized to facilitate weight gain and impede weight loss. Unique among known animal peptides, the serine-3 residue of ghrelin is posttranslationally acylated with an n-octanoic acid, a modification important for the peptide's active blood-brain transport and growth hormone secretagogue receptor-1 agonist activity. Pharmacological degradation of ghrelin would be hypothesized to reduce ghrelin's biological effects. To study endogenous ghrelin's role in appetite and energy expenditure, we generated antibodies that hydrolyze the octanoyl moiety of ghrelin to form des-acyl ghrelin. The most proficient antibody catalyst, GHR-11E11, was found to display a second-order rate constant of 18 M ؊ 1⅐s ؊1 for the hydrolysis of ghrelin to des-acyl ghrelin. I.v. administration of GHR-11E11 (50 mg/kg) maintained a greater metabolic rate in fasting C57BL/6J mice as compared with mice receiving a control antibody and suppressed 6-h refeeding after 24 h of food deprivation. Indirect respiratory measures of metabolism after refeeding and relative fuel substrate utilization were unaffected. The results support the hypothesis that acylated ghrelin stimulates appetite and curbs energy expenditure during deficient energy intake, whereas des-acyl ghrelin does not potently share these functions. Catalytic anti-ghrelin antibodies might thereby adjunctively aid consolidation of caloric restrictioninduced weight loss and might also be therapeutically relevant to Prader-Willi syndrome, characterized after infancy by hyperghrelinemia, hyperphagia, and obesity.hormone inactivation ͉ obesity ͉ neuropeptides A pproximately 1 billion people worldwide are overweight or obese (body mass index ϭ 25-29.9 or Ͼ30 kg/m 2 , respectively) (1), conditions associated with significant morbidity and mortality and for which new treatments are needed (2). Among recently characterized molecules implicated in energy homeostasis, ghrelin was identified in 1999 during a search for the endogenous ligand for the GH secretagogue receptor (GHSR) (ghrelin receptor), previously localized to peripheral tissues and to several CNS sites, including the arcuate nucleus and ventromedial hypothalamic nucleus (3). Human ghrelin is a 28-amino acid acylated peptide (GSS(n-octanoyl)FLSPEHQRVQQRKESKKPPAKLQPR) released mainly from endocrine cells of the stomach and upper gastrointestinal tract but also expressed in testes, kidney, pituitary, pancreas, lymphocytes, and brain (3-7). Several findings establish gastric ghrelin as an indicator of energy insufficiency and anabolic modulator of energy homeostasis (3). Ghrelin secretion is thought to stimulate food intake, slow metabolic rate, and spare lipid oxidation via central (8) and, possi...

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Short‐Term Effects of Gastric Bypass Surgery on Circulating Ghrelin Levels

Cited by 99 publications

References 47 publications

Meal suppression of circulating ghrelin is normalized in obese individuals following gastric bypass surgery

Meal suppression of circulating ghrelin is normalized in obese individuals following gastric bypass surgery

Ghrelin levels before and after reduction of overweight due to a low-fat high-carbohydrate diet in obese children and adolescents

Catalytic antibody degradation of ghrelin increases whole-body metabolic rate and reduces refeeding in fasting mice

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