Relationships between desacylated and acylated ghrelin and insulin sensitivity in the metabolic syndrome.
BACKGROUND
Metabolic syndrome shows clustered metabolic abnormalities with major roles for insulin resistance and obesity. Ghrelin is a gastric hormone whose total plasma concentration (T-Ghr) is associated positively with insulin sensitivity and is reduced in obesity. Ghrelin circulates in acylated (A-Ghr) and desacylated (D-Ghr) forms, but their potential differential associations with insulin resistance and whether they are differentially altered in obesity remain undefined.


OBJECTIVE
Our objective was to determine potential differential associations of ghrelin forms with insulin resistance [homeostasis model assessment of insulin resistance (HOMA-IR)] and the impact of obesity on their plasma concentrations in metabolic syndrome.


METHODS
This is a cross-sectional study.


METHODS
The study was performed in a metabolic outpatient unit.


METHODS
Patients with metabolic syndrome (National Cholesterol Education Program-Adult Treatment Panel III; n = 45, 23 males/22 females) were included in the study.


RESULTS
The main study outcomes were metabolic syndrome criteria, HOMA-IR, and ghrelin forms.


RESULTS
Plasma insulin and HOMA-IR were associated negatively with T-Ghr and D-Ghr but positively with A-Ghr and acylated to desacylated ghrelin (A/D-Ghr) ratio (n = 45; P < 0.05). Compared with nonobese [body mass index (BMI) < 27.5 kg/m(2); n = 12, six males/six females], obese metabolic syndrome patients (BMI > 27.5 kg/m(2); n = 33) had lower T-Ghr and D-Ghr but comparable A-Ghr and higher A/D-Ghr ratio (P < 0.05). BMI and waist circumference (WC) were positively related with HOMA-IR (n = 45; P < 0.05). However, opposite associations between A/D-Ghr ratio and HOMA-IR remained significant after adjustment for sex and BMI (or WC). Additional obese individuals without metabolic syndrome (n = 10: age-, sex-, BMI-, and WC-matched to obese metabolic syndrome patients) had lower T-Ghr but higher A-Ghr (P < 0.05) compared with age-, sex-matched healthy nonobese counterparts (n = 15). T-Ghr and A-Ghr were comparable in obese with or without metabolic syndrome.


CONCLUSIONS
Obesity could alter circulating ghrelin profile, and relative A-Ghr excess could contribute to obesity-associated insulin resistance in metabolic syndrome.
Barazzoni
Rocco
R
Clinica Medica, Department of Clinical, Morphological and Technological Sciences, University of Trieste, Ospedale Cattinara, Strada di Fiume 447, 34127 Trieste, Italy. barazzon@units.it
Zanetti
Michela
M
Ferreira
Clara
C
Vinci
Pierandrea
P
Pirulli
Alessia
A
Mucci
Mariapia
M
Dore
Franca
F
Fonda
Maurizio
M
Ciocchi
Beniamino
B
Cattin
Luigi
L
Guarnieri
Gianfranco
G
D000215:Acylation; D000886:Anthropometry; D008076:Cholesterol, HDL / Q000097:blood; D003430:Cross-Sectional Studies; D005260:Female; D054439:Ghrelin / Q000097:blood / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D024821:Metabolic Syndrome / Q000378:metabolism*; D008875:Middle Aged; D015999:Multivariate Analysis; D009765:Obesity / Q000378:metabolism*; D012044:Regression Analysis; D014280:Triglycerides / Q000097:blood
D008076:Cholesterol, HDL; D054439:Ghrelin; D014280:Triglycerides