Ghrelin restores ‘lean-type’ hunger and energy expenditure profiles in morbidly obese subjects but has no effect on postgastrectomy subjects

Abstract

Objective: To examine the effects of ghrelin on appetite and energy expenditure in lean, obese and postgastrectomy subjects. Design: A randomized, double-blind, placebo-controlled study. Patients: Nine lean subjects (mean body mass index (BMI) 23.5±3 kg/m 2 ) and nine morbidly obese subjects (mean BMI 51.4 ± 10 kg/m 2 ) and eight postgastrectomy subjects (mean BMI 22.4 ± 1.0 kg/m 2 ). Interventions: Subjects were infused with either intravenous ghrelin (5 pmol kg À1 min À1 ) or saline over 270 min. They were given a fixed energy breakfast followed by a free buffet lunch towards the end of the infusion. Main outcome measures: Visual analogue scales were used to record hunger and energy expenditure was measured by indirect calorimetry. Results: Ghrelin increased energy intake at the buffet lunch in lean subjects (a 41% increase, Po0.01) and obese subjects (35% increase, P ¼ 0.04) but not in postgastrectomy subjects. Lean subjects showed a characteristic preprandial rise and postprandial fall in hunger scores, which was exaggerated by ghrelin infusion. Obese subjects showed little variation in hunger scores, but a 'lean-type' pattern was restored when given exogenous ghrelin. Ghrelin had no effect on resting metabolic rate but did increase respiratory quotient (RQ) in obese subjects. Ghrelin also increased RQ variability over time in all three groups (ANOVA, Po0.001). Conclusions: Hunger scores are abnormal in the obese, perhaps because of impaired ghrelin secretion. The effect of ghrelin in restoring normal hunger profiles in the obese suggests causality, confirming an important role in eating behaviour. Ghrelin also increases RQ in obese humans and increased RQ variability in all groups. This suggests that ghrelin regulates substrate utilization and may promote metabolic flexibility.

Impaired oxidative capacity due to decreased CPT1b levels as a contributing factor to fat accumulation in obesity

“…Interestingly, obese humans are not ghrelin resistant as increased food intake and hunger ratings were observed after infusion of 5 pmol·kg Ϫ1 ·min Ϫ1 ghrelin for 75 min in both obese and lean subjects (11). Also, very obese subjects (mean body mass index 51.4) responded similarly to ghrelin infusions with respect to food intake as lean subjects (19). We did not observe full ghrelin resistance in the OR rats despite long-term Western diet feeding, supporting that diet per se does not cause ghrelin resistance.…”

Ghrelin Gene Products and the Regulation of Food Intake and Gut Motility

“…Therefore, the assumption that systemic total ghrelin levels reflect acyl ghrelin secretion should be made with caution (Gauna et al, 2007). For instance, fasting plasma total ghrelin (Cummings et al, 2002a;English et al, 2002;Rigamonti et al, 2002;Shiiya et al, 2002;Erdmann et al, 2005;Korner et al, 2005Korner et al, , 2006le Roux et al, 2005b;Engström et al, 2007;Guo et al, 2007;Vicennati et al, 2007;Huda et al, 2009;), des-acyl ghrelin (Rodríguez et al, 2009), and obestatin (Guo et al, 2007;Nakahara et al, 2008) concentration were lower in obese than lean subjects, whereas acyl ghrelin concentration was higher in obese persons (Rodríguez et al, 2009). In addition, obese persons showed lower expression of GHS-R in omental adipose tissue (Rodríguez et al, 2009).…”

Attenuating the Biologic Drive for Weight Regain Following Weight Loss: Must What Goes Down Always Go Back Up?

“…In lean individuals, plasma ghrelin concentrations rise during fasting and drop with meal ingestion proportional to the calorie content of the meals [48]. Obese individuals may not display the same suppression of ghrelin in response to calorie ingestion [49,50]. Weight loss leads to an elevation of plasma ghrelin in obese adolescents [51] and adults [52], which is thought to be a compensatory adjustment designed to increase energy intake in an attempt to return body fat stores to their initial levels.…”