Increased Density of Ghrelin-Expressing Cells in the Gastric Fundus and Body in Prader-Willi Syndrome

Abstract

Context:The levels of ghrelin, an orexigenic hormone secreted by oxyntic cells in the digestive tract, are elevated in Prader-Willi syndrome (PWS) and GH deficiency (GHD) patients. In this study, we hypothesized that the hyperghrelinemia observed in PWS is related to IGF-I or GH/IGF axis deficiency. Design:We investigated the densities of ghrelin-expressing cells (GECs), the amounts of ghrelin in gastric tissues, and ghrelin levels in plasma in 16 PWS patients and compared these results with those of 13 GHD patients and comparison groups (19 normal lean and 10 normal obese subjects). Results:In the gastric body and fundus, 2-to 3-fold increases in the numbers of GECs (P Ͻ 0.001) and in the amounts of ghrelin (P Ͻ 0.018) were noted in PWS patients vs. comparison groups, whereas GEC numbers in GHD patients were similar to those of the comparison group despite elevated fasting plasma ghrelin levels. In addition, IGF-I SD scores in PWS were not found to be correlated with GEC densities, the amounts of ghrelin expressed in gastric tissues, or plasma ghrelin levels. Conclusions:Our results suggest that IGF-I or GH/IGF axis deficiency appears to be unrelated to observed GEC increases in the stomach of patients with PWS. G HRELIN IS AN acylated peptide that is secreted byA-like endocrine cells of the oxyntic mucosa of the stomach and induces the secretion of GH (1, 2). Removing the acid-producing portion of the stomach was found previously to reduce circulating ghrelin by 80%, supporting the notion that the oxyntic mucosa is the major source of circulating ghrelin (3). Ghrelin can induce acute hunger, increase food intake, and reduce fat utilization in rodents and humans (1, 4). However, the direct orexigenic effect of ghrelin in its physiologic concentration range has not been elucidated in rodents or humans.Prader-Willi syndrome (PWS) is the most common form of human syndromic obesity. Ghrelin levels have been reported to be elevated in PWS (5-7). Moreover, unlike normal obese individuals, who have low fasting-plasma ghrelin concentrations, PWS patients can have 3-to 4-fold higher ghrelin fasting concentrations (5-7). Elevated plasma ghrelin levels in PWS may be related to low plasma insulin levels, because insulin plays an important role in the suppression of plasma ghrelin (8 -10).Recently, plasma ghrelin levels were reported to be elevated in patients with GH deficiency (GHD) (11,12). Because some PWS patients show attenuated plasma GH levels, and because total and free IGF-I have been reported to be low in PWS compared with obese individuals, partial GHD may also contribute to the hyperghrelinemia in PWS.In the present study, we hypothesized that the hyperghrelinemia observed in PWS is related to IGF-I or GH/IGF axis deficiency. We investigated plasma ghrelin levels, ghrelin-expressing cell (GEC) densities, and ghrelin quantities in the gastric tissues of PWS and GHD patients and in those of lean and obese normal subjects and correlated these results with total IGF-I levels. We found that GEC densities and ghreli...

Exendin-4 Potently Decreases Ghrelin Levels in Fasting Rats

“…Indeed, it has been established that the levels of circulating ghrelin are strongly elevated in the plasma of patients with PWS due to an increase in ghrelin-producing cells in the stomach (7,8,49). Thus, it has been proposed that ghrelin might play a significant or indeed crucial role in the pathogenesis of this still incurable disease (8).…”

Metabolic Parameters and Orexigenic/Anorexigenic Factors of Obesity in Prader-Willi Syndrome

“…The cause of hyperghrelinemia in PWS is unclear. There are data, suggesting that PWS patients have the increased number of ghrelin-expressing cells in gastric tissue [7]. In addition, relative hypoinsulinemia and/or increase in insulin sensitivity may act as an additive signal to enhance hyperghrelinemia in PWS (as insulin has an inhibitory role on ghrelin secretion) [8].…”

Hyperghrelinemia in the patients presenting with Prader-Willi syndrome

“…Обследованы 42 пациента (14 мальчиков, 28 де-вочек) в возрасте от 1,5 до 15 лет, медиана 9,8 (6,(5)(6)(7)(8)(9)(10)(11)8) года. В 1-ю группу включены 17 детей (6 мальчиков, 11 девочек) с СПВ (SDSимт=3,6 (2,99-4,57) в воз-расте 9,9 (6,5-13,9) года, во 2-ю группу -15 паци-ентов (4 мальчика, 11 девочек) с конституциональ-но-экзогенным ожирением (КЭО) в возрасте 9,8 (6,5-12,0) года (SDSимт=3,3 (2,76-3,62) и в 3-ю ПРОБЛЕМЫ ЭНДОКРИНОЛОГИИ, 3,2014 группу -10 практически здоровых детей (4 мальчи-ка, 6 девочек) с нормальной массой тела (SDSимт 0,75 (-0,69-1,27), в возрасте 9,7 (7,05-10,7) года (см.…”

“…По мнению Y. Сhoe и соавт. [10], одной из причин препрандиальной гипергрелинемии при СПВ мо-жет являться гиперплазия клеток, секретирующих грелин, так как в теле и дне желудка у пациентов с СПВ содержание этих клеток в 2-3 выше по срав-нению с контрольной группой (р<0,018) [37].…”

“…К настоящему вре-мени причины такой гиперфагии неизвестны и из-учаются различные патогенетические механизмы ее возникновения. *e-mail: light2307@mail.ru Грелин является единственным известным пе-риферическим орексигенным пептидом, который стимулирует повышенное потребление пищи и сни-жает утилизацию жира как у животных, так и у лю-дей [10][11][12]; секретируется в основном эндокрин-ными клетками фундальных желез желудка [13,14]. Уровни циркулирующего грелина повышаются не-задолго до каждого приема пищи и снижаются по-сле еды или введения глюкозы [15,16].…”