The Relationship between Active Ghrelin Levels and Human Obesity Involves Alterations in Resting Energy Expenditure

Abstract

Ghrelin is a gastric hormone that exerts a stimulatory effect on appetite and fat accumulation. Ser(3) octanoylation is regarded as a prerequisite for ghrelin biological activity, although des-octanoylated forms may retain biological functions in vitro. Circulating ghrelin levels are usually low in obesity and in states of positive energy balance. Hence, the aim of our study was to analyze plasma active and serum total ghrelin levels in 20 obese (ages, 22-42 yr; body mass index, 41.3 +/- 1.1 kg/m(2)) and 20 lean subjects (ages, 22-43 yr; body mass index, 22.4 +/- 0.6 kg/m(2)) as well as their relationship to measures of glucose homeostasis, body fat, and resting energy expenditure (REE). The measured/predicted REE percentage ratio was calculated to subdivide groups into those with positive (> or = 100% ) and negative (<100%) ratio values. In obese patients, plasma active (180 +/- 18 vs. 411 +/- 57 pg/ml; P < 0.001) and serum total ghrelin levels (3650 +/- 408 vs. 5263 +/- 643 pg/ml; P < 0.05) were significantly lower when compared with lean subjects. Hence, ghrelin activity, defined as the proportion of active over total ghrelin levels, was similarly reduced in the obese state (6.1 +/- 0.9% vs. 8.4 +/- 1%; P < 0.05). There was a significant correlation between active and total ghrelin (r = 0.62; P < 0.001), and between total ghrelin and insulin (r = -0.53; P < 0.001) or insulin resistance using the homeostatis model of assessment-insulin resistance (r = -0.49; P < 0.001) approach. Significantly higher active ghrelin levels (214 +/- 22 vs. 159 +/- 30 pg/ml; P < 0.05) and ghrelin activity (8 +/- 1.7% vs. 4.9 +/- 0.9%; P < 0.05) were observed in patients with positive compared with negative measured/predicted REE ratio values. Our study shows that obesity is associated with an impairment of the entire ghrelin system. The observation that ghrelin is further decreased in cases of abnormal energy profit adds new evidence to the relationship between ghrelin activity and energy balance in obesity.

Acylated and desacyl ghrelin stimulate lipid accumulation in human visceral adipocytes

“…[2][3][4] However, the potential differences between the different ghrelin forms under these pathophysiological conditions are controversial and remain largely undefined. [34][35][36][37][38] As expected, our data show decreased plasma desacyl ghrelin levels in obese patients, which is in accordance with studies carried out by other authors. [34][35][36][37][38] Nonetheless, we found, for the first time, that plasma acylated ghrelin levels are increased in obesity and obesity-associated T2D.…”

“…[34][35][36][37][38] As expected, our data show decreased plasma desacyl ghrelin levels in obese patients, which is in accordance with studies carried out by other authors. [34][35][36][37][38] Nonetheless, we found, for the first time, that plasma acylated ghrelin levels are increased in obesity and obesity-associated T2D. The elevation of circulating acylated ghrelin concentrations in obese individuals may play a role in obesity-associated hyperphagia and adiposity.…”

Subcutaneous administration of ghrelin stimulates energy intake in healthy lean human volunteers

“…11 Plasma-acylated ghrelin was quantified using the active ghrelin Linco RIA (product no GHRA-88HK). 12 In order to confirm the bioactivity of ghrelin administered subcutaneously, plasma GH was analysed with the Advantage automated chemiluminescent immunoassay (Nichols Institute Diagnostics).…”

Circulating levels of active ghrelin is associated with abdominal adiposity, hyperinsulinemia and insulin resistance in patients with type 2 diabetes mellitus

“…Recently, it became possible to measure the biologically active form of ghrelin in plasma (12 -14). Marzullo et al has reported that the circulating level of active ghrelin is decreased in obese subjects and that it is significantly correlated with BMI, but not with serum levels of insulin or insulin resistance in nondiabetic subjects (14). However, the relationship between plasma levels of active ghrelin and abdominal adiposity, serum levels of insulin or insulin resistance has not yet been reported in type 2 diabetic patients.…”