Predictors of Postabsorptive Ghrelin Secretion after Intake of Different Macronutrients

Abstract Context: Release of ghrelin, a gastrointestinal hormone regulating feeding and energy balance, is blunted in obesity, a condition associated with insulin resistance. Objective: The objective was to identify anthropometric and metabolic predictors of postabsorptive ghrelin secretion. Design: We evaluated ghrelin, insulin, glucose, and leptin secretion overnight and after intake of different macronutrients. Subjects: Ten obese subjects (age, 31.8 ± 2.5 yr; body mass index, 43.4 ± 0.8 kg/m2) and six lean subjects (age, 33.5 ± 2.4 yr; body mass index, 21.8 ± 1.4 kg/m2) participated in the study. Main Outcome Measures: The main outcome measures were resting energy expenditure (REE); fat mass; nighttime approximate entropy (ApEn) and synchronicity (cross-ApEn) of ghrelin, insulin, and leptin; insulin sensitivity by homeostatic model approach insulin-sensitivity (HOMA-S%); postabsorptive area under the curve (AUC); and Δ of ghrelin, insulin, glucose, and leptin after carbohydrate-, lipid-, and protein-rich test meals. Results: Nighttime ApEn scores were higher in obese than lean subjects (P < 0.01). Cross-ApEn revealed a synchronicity between ghrelin-insulin, ghrelin-leptin, and insulin-leptin in both groups. Compared with baseline, ghrelin decreased significantly (P < 0.01) in lean and obese subjects after carbohydrates (42.2 vs. 28.5%; P < 0.05), lipids (40.2 vs. 26.2%; P < 0.01), and proteins (42.2 vs. 26.3%; P < 0.01) devoid of between-meal ghrelin differences. Significant associations occurred between nocturnal ghrelin ApEn and insulin (r = 0.53; P < 0.05), postmeal ghrelin AUCs and REE (r = −0.57; P < 0.05), and HOMA-S% (r = 0.52; P < 0.05), postmeal ghrelin Δ and HOMA-S% (r = 0.60; P < 0.05). REE (β = −0.57; P = 0.02) and ghrelin ApEn (β = −0.62; P = 0.01) were predictors of postmeal ghrelin AUC and Δ, respectively. Conclusions: Obesity determined a decreased orderliness of ghrelin secretion and a relative loss of ghrelin-insulin synchrony. Postabsorptive ghrelin secretion decreased significantly both in obese and lean subjects, was related to insulin sensitivity, and was predicted by energy expenditure and hormone pulsatility

Safety and efficacy of therapy with botulinum toxin in obesity: a pilot study

none8noBackground: Botulin toxin (BTX) has been proposed as a potential obesity treatment. Methods: In a pilot study, the short-term efficacy and safety of BTX was assessed in eight subjects (four men, four women; median age, 46 years; range, 35-57 years) with severe obesity (median body mass index [BMI], 47.1 kg/m(2); range 38.2-56.7 kg/m(2)) and multiple dietary treatment failures. In a single endoscopic session, 500 UI of BTX-A was injected in the gastric antral region. Results: No clinically significant side effects were observed. In all patients, despite their not being on a specific diet, a reduction of body weight was observed at 1 month (median baseline weight, 124.4 kg vs 121.8 kg at 1 month; P < 0.05). Two treatment-unrelated dropouts were observed. At 4 months, three of the six patients had a further weight loss. The treatment effect was apparently independent of changes in hunger or satiety, or of changes in fasting and postprandial plasma ghrelin and serum leptin, thus suggesting a different pharmacological mechanism. Conclusions: BTX-A treatment appears to be safe and well tolerated by obese patients, while its short-term efficacy varied widely.mixedAlbani G; PETRONI M; Mauro A; Liuzzi A; Lezzi G; Verti B; Marzullo P; Cattani LAlbani G; PETRONI M; Mauro A; Liuzzi A; Lezzi G; Verti B; Marzullo P; Cattani

Safety and efficacy of therapy with botulinum toxin in obesity: a pilot study

Background: Botulin toxin (BTX) has been proposed as a potential obesity treatment. Methods: In a pilot study, the short-term efficacy and safety of BTX was assessed in eight subjects (four men, four women; median age, 46 years; range, 35-57 years) with severe obesity (median body mass index [BMI], 47.1 kg/m(2); range 38.2-56.7 kg/m(2)) and multiple dietary treatment failures. In a single endoscopic session, 500 UI of BTX-A was injected in the gastric antral region. Results: No clinically significant side effects were observed. In all patients, despite their not being on a specific diet, a reduction of body weight was observed at 1 month (median baseline weight, 124.4 kg vs 121.8 kg at 1 month; P < 0.05). Two treatment-unrelated dropouts were observed. At 4 months, three of the six patients had a further weight loss. The treatment effect was apparently independent of changes in hunger or satiety, or of changes in fasting and postprandial plasma ghrelin and serum leptin, thus suggesting a different pharmacological mechanism. Conclusions: BTX-A treatment appears to be safe and well tolerated by obese patients, while its short-term efficacy varied widely

Sporadic mutations in melanocortin receptor 3 in morbid obese individuals

Several mutations in the melanocortin receptor 4 gene have been identified in humans and account for 3 - 6% of morbid obesity. In contrast, strong evidence of a causative role for melanocortin receptor 3 ( MC3R) mutations are still lacking. In MC3R knockout mice, high feed efficiency rather than hyperphagia seems to contribute to increased fat mass. On the basis of this evidence, the objective of the present study was to investigate the presence of MC3R mutations in a group of 290 obese subjects ( mean BMI 44.2 +/- 5.9 kg/m(2)). As a control, a group of 215 normal-weight subjects ( mean BMI 22.4 +/- 2.7 kg/m(2)) was also screened. Three novel mutations in the MC3R gene ( A293T, I335S and X361S) were identified among the obese patients. The mutations segregated with obesity in the members of the families studied. In vitro expression studies of each mutation demonstrated a loss of function of the 1335S- mutated receptor. These findings suggest that, in humans, MC3R mutations may be a cause of a dominantly inherited form of obesity. However, this association as well as the specific phenotypic characteristics resulting from these mutations need to be further evaluated in larger series of obese subjects