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Expression of ghrelin gene in peripheral blood mononuclear cells and plasma ghrelin concentrations in patients with metabolic syndrome.

¹ Department of Clinical Nutrition, School of Public Health and Clinical Nutrition, Food and Health Research Centre, University of Kuopio PO Box 1627, FIN-70211 Kuopio, Finland² Institute of Clinical Medicine, Internal Medicine, University of Kuopio and Kuopio University Hospital, PO Box 1777, FIN-70211 Kuopio, Finland³ Department of Internal Medicine, Federal University of Rio Grande do Sul, 90035-003 Porto Alegre, Brazil⁴ Kuopio Research Institute of Exercise Medicine, Kuopio, Finland⁵ Institute of Biomedicine, Physiology, University of Kuopio, PO Box 1627, FIN-70211 Kuopio, Finland

(Correspondence should be addressed to U Mager who is now at School of Public Health and Clinical Nutrition, University of Kuopio, Mediteknia Building, PO Box 1627, FIN-70211 Kuopio, Finland; Email: ursula.mager{at}uku.fi)

Objective: We examined the expression of ghrelin and ghrelin receptors in peripheral blood mononuclear cells (PBMCs) and evaluated the effect of weight loss or exercise on plasma ghrelin concentrations in subjects with the metabolic syndrome.

Design and methods: Data from 75 overweight/obese subjects randomized to a weight loss, aerobic exercise, resistance exercise or control group for a 33-week intervention period were analysed. The plasma ghrelin concentrations and indices of insulin and glucose metabolism were assessed, and mRNA expression of ghrelin, its receptors and various cytokines in PBMCs was studied using real-time PCR.

Results: Ghrelin and GH secretagogue receptor 1b were expressed in PBMCs of subjects with metabolic syndrome. Ghrelin gene expression correlated positively with the expressions of tumour necrosis factor- (P<0.001), interleukin-1β (P<0.001) and interleukin-6 (P=0.026) during the study, but was not associated with the plasma ghrelin concentration. Genotype-specific ghrelin gene expression in PBMCs was found for the –604G/A and the –501A/C polymorphisms in the ghrelin gene. At baseline, the plasma ghrelin levels were associated with fasting serum insulin concentrations, insulin sensitivity index and high-density lipoprotein cholesterol. However, longitudinally weight, BMI or waist circumference and acute insulin response in i.v. glucose tolerance test were stronger predictors of the ghrelin concentration. Plasma ghrelin did not change over the study period in the weight reduction group, but it tended to decrease in the control group (P=0.050).

Conclusions: Ghrelin mRNA expression in PBMCs suggests an autocrine role for ghrelin within an immune microenvironment. Moderate long-term weight loss may prevent a decline in ghrelin concentration over time in individuals with metabolic syndrome.