Objective: Ghrelin [acylated (AG) and nonacylated (NAG)] has been shown to play a pivotal role in the regulation of food intake and insulin sensitivity. It is presently unclear whether variation in insulin sensitivity is related to AG and NAG levels in obese individuals. To address this issue, we determined whether insulin-sensitive overweight or obese (ISO) and insulin-resistant overweight or obese (IRO) individuals display different total ghrelin (TotG), AG, and NAG profiles during a euglycemic/hyperinsulinemic clamp (EHC).Design: Eighty-nine nondiabetic overweight and obese postmenopausal women underwent EHC to evaluate insulin sensitivity. Body composition and blood lipid profiles were assessed. Subjects within the highest tertile of insulin sensitivity were described as ISO (n ϭ 31), whereas those within the lowest tertile of insulin sensitivity were considered as IRO (n ϭ 29). Plasma TotG, AG, and NAG profiles were assessed by RIA at 0, 60, 160, 170, and 180 min during the EHC.Results: TotG and NAG levels were significantly decreased for ISO and IRO individuals during the EHC, whereas only ISO subjects displayed a significant reduction of AG concentrations (P Ͻ 0.05). AG area under the curve value and the ratio of AG/NAG (fasting and area under the curve) were significantly decreased in ISO individuals. Furthermore, maximal reduction of TotG and AG concentrations was greater in ISO compared with IRO individuals (P Ͻ 0.05). Insulin sensitivity was significantly correlated with maximal reduction of TotG (r ϭ 0.36; P Ͻ 0.01) and AG (r ϭ 0.36; P Ͻ 0.05) concentrations. Conclusion:The dysregulation of ghrelin secretion profiles during EHC is associated with insulin resistance. AG may contribute to the variation of insulin sensitivity in overweight or obese postmenopausal women. (J Clin Endocrinol Metab 92: 264 -269, 2007) G HRELIN, A PEPTIDE mainly derived from the stomach, plays important roles in the regulation of food intake as well as energy metabolism and storage (1). Emerging evidence suggests that nonacylated and acylated ghrelin forms (2) may induce different physiological and metabolic effects. Moreover, acylated ghrelin is the endogenous ligand of the GH secretagogue receptor 1a, whereas recent reports indicate that nonacylated ghrelin may interact with another uncharacterized receptor (3-6). Interestingly, numerous studies have suggested that total ghrelin (nonacylated ϩ acylated ghrelin) is closely linked to insulin resistance (7). In humans, acute [postprandial and euglycemic/hyperinsulinemic clamp (EHC)] and chronic (insulin resistance) hyperinsulinemic states are associated with decreased circulating total ghrelin levels (8 -10). However, the regulation of acylated vs. nonacylated ghrelin in these conditions still remains poorly understood. In addition, as reported by McLaughlin et al. (11), insulin-sensitive individuals display higher fasting total ghrelin concentrations than insulinresistant obese subjects. Furthermore, when compared with insulin-resistant obese subjects, insulin-sensitive norm...

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Background/Objectives: To analyze the anthropometric, metabolic, psychosocial and dietary profiles of underreporters, identified by the doubly labeled water technique, in a well-characterized population of overweight and obese postmenopausal women. Subjects/Methods: The study population consisted of 87 overweight and obese sedentary postmenopausal women (age: 57.7±4.8 years, body mass index: 32.4±4.6 kg/m 2 ). Subjects were identified as underreporters based on the energy intake to energy expenditure ratio of o0.80. We measured (1) body composition (by dual-energy X-ray absorptiometry), (2) visceral fat (by computed tomography), (3) blood profile, (4) resting blood pressure, (5) peak oxygen consumption (VO 2 peak ), (6) total energy expenditure, (7) muscle strength and (8) psychosocial and dietary profiles. Results: Out of 87 subjects, 50 (57.5%) were identified as underreporting subjects in our cohort. Underreporters showed higher levels of body mass index, fat mass, visceral fat, hsC-reactive protein, perceived stress and percentage of energy from protein, as well as lower levels of VO 2 peak , dietary intake of calcium, fiber, iron, vitamin B-1 and 6, as well as servings of fruit and vegetables. Logistic regression analysis showed that fat mass, odd ratio 1.068 (95% confidence interval 1.009-1.130) and perceived stress, odd ratio 1.084 (95% confidence interval 1.011-1.162) were independent characteristics of underreporters. Conclusions: Results from this study show significant differences in anthropometric, metabolic, psychosocial and dietary profiles between underreporters and non-underreporters in our cohort of overweight and obese postmenopausal women.

The purpose of this study was to examine the psychosocial correlates of cardiorespiratory fitness (VO2peak) and muscle strength in overweight and obese sedentary post-menopausal women. The study population consisted of 137 non-diabetic, sedentary overweight and obese post-menopausal women (mean age 57.7 years, s = 4.8; body mass index 32.4 kg.m(-2), s = 4.6). At baseline we measured: (1) body composition using dual-energy X-ray absorptiometry; (2) visceral fat using computed tomography; (3) insulin sensitivity using the hyperinsulinaemic-euglycaemic clamp; (4) cardiorespiratory fitness; (5) muscle strength using the leg press exercise; and (6) psychosocial profile (quality of life, perceived stress, self-esteem, body-esteem, and perceived risk for developing chronic diseases) using validated questionnaires. Both VO2peak and muscle strength were significantly correlated with quality of life (r = 0.29, P < 0.01 and r = 0.30, P < 0.01, respectively), and quality of life subscales for: physical functioning (r = 0.28, P < 0.01 and r = 0.22, P < 0.05, respectively), pain (r = 0.18, P < 0.05 and r = 0.23, P < 0.05, respectively), role functioning (r = 0.20, P < 0.05 and r = 0.24, P < 0.05, respectively), and perceived risks (r = -0.24, P < 0.01 and r = -0.30, P < 0.01, respectively). In addition, VO2peak was significantly associated with positive health perceptions, greater body esteem, and less time watching television/video. Stepwise regression analysis showed that quality of life for health perceptions and for role functioning were independent predictors of VO2peak and muscle strength, respectively. In conclusion, higher VO2peak and muscle strength are associated with a favourable psychosocial profile, and the psychosocial correlates of VO2peak were different from those of muscle strength. Furthermore, psychosocial factors could be predictors of VO2peak and muscle strength in our cohort of overweight and obese sedentary post-menopausal women.

Objective: Recent reports have suggested that the existence of associations between hormonal dysregulation and chronic upregulation of inflammatory markers, which may cause obesity-related disturbances. Thus, we examined whether acylated ghrelin (AcylG) and total ghrelin (TotG) levels could be associated with the following inflammatory markers: C-reactive protein (CRP), tumor necrosis factor a (TNF-a), and soluble TNF receptor 1 (sTNF-R1). Design: Cross-sectional study consisting of 50 overweight and obese postmenopausal women. Methods: AcylG and TotG levels were assessed at 0, 60, 160, 170, and 180 min of the euglycemic/hyperinsulinemic clamp (EHC). We evaluated insulin sensitivity, body composition, and blood lipid profiles as well as fasting concentrations of CRP, TNF-a, and sTNF-R1. Results: In fasting conditions, sTNF-R1 was negatively correlated with AcylG (rZK0.48, P!0.001) levels. In addition, AcylG/TotG was associated negatively with sTNF-R1 (rZK0.44, PZ0.002) and positively with TNF-a (rZ0.38, PZ0.009) values. During the EHC, TotG (at all time points) and AcylG (at 60 and 160 min) values were significantly decreased from fasting concentrations. AcylG maximal reduction and area under the curve (AUC) values were correlated to sTNF-R1 (rZK0.35, PZ0.02 and rZK0.34, PZ0.02, respectively). Meanwhile, the AcylG/TotG AUC ratio was associated negatively with sTNF-R1 (rZK0.29, P!0.05) and positively with TNF-a (rZ0.36, PZ0.02). Following adjustments for total adiposity, sTNF-R1 remained correlated with fasting and maximal reduction AcylG values. Similarly, AcylG/TotG ratios remained significantly correlated with sTNF-R1 and TNF-a. Importantly, 23% of the variation in sTNF-R1 was independently predicted by fasting AcylG. Conclusion: These results are the first to suggest that both fasting and EHC-induced AcylG profiles are correlated with fasting values of sTNF-R1, a component of the TNF-a system. Thus, AcylG may act, at least in part, as one mediator of chronic inflammatory activity in human obesity. European Journal of Endocrinology 157 419-426