The Decrease in Plasma Ghrelin Concentrations following Bariatric Surgery Depends on the Functional Integrity of the Fundus

Frühbeck, Gema; Díez-Caballero, A; Gil, Marı́a J.; Montero, I.; Gómez-Ambrosi, Javier; Salvador, Javier; Cienfuegos, Javier A.

doi:10.1381/096089204323093363

Cited by 149 publications

(98 citation statements)

References 36 publications

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“…With some knowledge regarding the possible mechanism of action of diversionary bariatric surgery some surgeons are targeting areas of Systematic review of fat-free mass loss TB Chaston et al hormonal importance, particularly ghrelin production. 62 Alterations in ghrelin levels are subject to the surgical technique with BPD, RYGB and more recently sleeve gastrectomy. Reduced postoperative levels of this important growth hormone secretagogue may result in excessive loss of FFM.…”

Section: Discussionmentioning

confidence: 99%

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Changes in fat-free mass during significant weight loss: a systematic review

2006

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Objective: To identify the proportion of weight lost as fat-free mass (FFM) by various weight loss interventions. Methods: Medline and Embase were systematically searched for reliable measurements of FFM before and after weight loss of 410 kg and eligible data were pooled. In a fixed effect model of % FFM loss/weight loss (%FFML), linear regression analysis was used to determine the influence of degree of caloric restriction, exercise, magnitude of weight loss, initial body mass index (BMI) and type of surgery. Results: Data were included from 26 cohorts treated with dietary and behavioral interventions and 29 cohorts of bariatric surgery patients. The degree of caloric restriction was positively associated with %FFML (r 2 ¼ 0.31, P ¼ 0.006) and in three randomized controlled trials exercise was shown to decrease %FFML. Compared with laparoscopic adjustable gastric banding (LAGB), biliopancreatic diversion (BPD) and roux en Y gastric bypass (RYGB) caused greater log e (natural log) %FFML (r 2 ¼ 0.453, Po0.001). Differences in log e %FFML between surgical procedures were independent of initial BMI and magnitude of weight loss. Conclusions: The degree of caloric restriction, exercise and rate of weight loss influence the proportion of weight lost as FFM after non-surgical interventions. For surgical interventions, BPD and RYGB result in greater %FFML than LAGB.

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Section: Discussionmentioning

confidence: 99%

“…Reduced postoperative levels of this important growth hormone secretagogue may result in excessive loss of FFM. 62,63 To date, quantitative definition of 'excessive loss of FFM' is lacking. An obvious way to set standards of %FFML is to use normative data to calculate appropriate fat and fat-free composition of weight loss.…”

Section: Discussionmentioning

confidence: 99%

Changes in fat-free mass during significant weight loss: a systematic review

2006

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“…Two further open studies 27,28 and a double-blind trial 29 extended this observation, but in the series of Garcia-Compean et al 27 no significant effects on body weight and gastric emptying were observed. As the fundus of the stomach is the main source of ghrelin 30 and has a sensory activity 31 regulating the total gastric capacity, we modified the technique described by Rollnik and included the fundus as a target area for BTX injection. Our results confirm the observation of Rollnik et al 26 and demonstrate, in a double-blind, placebocontrolled trial, that inhibition of the cholinomimetic synapses of the stomach in the antrum and fundus cause a reduction of the threshold of satiety in obese patients.…”

Section: Discussionmentioning

confidence: 99%

Treatment of morbid obesity by intraparietogastric administration of botulinum toxin: a randomized, double-blind, controlled study

et al. 2006

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Objective: The stomach is the main target organ for bariatric surgery, but no medical treatment has been developed to increase satiety and decrease food intake via gastric pathways. The aim of our study was to investigate whether or not the intraparietogastric administration of botulinum toxin A (BTX), able to modify the motility patterns of the stomach, could be useful for treatment of obesity. Design: Double blind controlled study. Subjects: Twenty-four morbidly obese patients (mean weight (s.e.m.) 116.174.89 kg, mean body mass index (BMI) 43.671.09 kg/m 2 ) were blindly randomized to receive 200 IU BTX or placebo into the antrum and fundus of the stomach by intraparietal endoscopic administration. Measurements: We evaluated weight loss, BMI changes, satiety score, the maximal gastric capacity for liquids and the gastric emptying time (octanoic acid breath test). Results: The two groups were homogeneous for anthropometric characteristics. Eight weeks after treatment, BTX patients had significantly higher weight loss (1171.09 vs 5.771.1 kg, Po0.001) and BMI reduction (470.36 vs 270.58 kg/m 2 , Po0.001) and a higher satiety score on a visual analogic scale (7.6370.38 vs 4.7270.44, Po0.001) than controls. Furthermore, BTX patients showed a significantly greater reduction in maximal gastric capacity for liquids (266.6748 vs 139731, Po0.001) and a greater prolongation in gastric emptying time ( þ 18.9378 vs À2.276.9 min, Po0.05). No significant side effects or neurophysiologic changes were found. Conclusions: Topical intragastric BTX was effective in reducing food intake and body weight in morbidly obese patients.

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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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The Decrease in Plasma Ghrelin Concentrations following Bariatric Surgery Depends on the Functional Integrity of the Fundus

Abstract: Fasting circulating ghrelin concentrations in patients undergoing diverse bariatric operations depend on the degree of dysfunctionality of the fundus.

Cited by 149 publications

References 36 publications

Changes in fat-free mass during significant weight loss: a systematic review

Changes in fat-free mass during significant weight loss: a systematic review

Treatment of morbid obesity by intraparietogastric administration of botulinum toxin: a randomized, double-blind, controlled study

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

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