Effect of diet-induced weight loss on plasma apelin and cytokine levels in individuals with the metabolic syndrome.

BACKGROUND AND AIMS: Adipose tissue is an active endocrine organ that secretes signaling molecules involved in the regulation of insulin sensitivity, food intake and inflammation. Apelin is a peptide secreted by adipose tissue that has been shown to modulate cardiovascular tone in animals. The aim of this study was to measure abdominal fat, blood pressure and circulating apelin, adiponectin, leptin, ghrelin, TNF-alpha and IL-6 levels in patients with the metabolic syndrome after a diet-induced weight loss. METHODS AND RESULTS: 35 obese individuals with the metabolic syndrome underwent an 8-week very-low-calorie diet (VLCD) and a 6-month weight maintenance period (WM) with 120mg orlistat or placebo administered 3 times daily. VLCD and WM (-15.1+/-1.0kg) decreased mean arterial pressure (MAP), insulin, leptin, triglycerides and visceral and subcutaneous adipose tissue. Moreover, adiponectin increased in response to the weight loss. However, the overall changes in plasma apelin, TNF-alpha and IL-6 were non-significant. A correlation between plasma apelin and TNF-alpha was observed at baseline (0.41, p<0.05), and the minor changes in plasma apelin levels were associated with changes in BMI during VLCD and MAP and TNF-alpha during VLCD and WM periods. CONCLUSION: Despite reductions in BMI, body adiposity, MAP and enhancement of glucose metabolism and adiponectin in response to weight loss, no significant changes in plasma apelin, TNF-alpha and IL-6 were observed. However, apelin significantly correlated with TNF-alpha and MAP. These results suggest that apelin may not be that strongly correlated with the fat mass as an adipokine like the more abundant adipokines adiponectin or leptin and it might be involved in the regulation of inflammation and cardiovascular tone.

Apelin, orexin-A and leptin plasma levels in morbid obesity and effect of gastric banding.

UNLABELLED: Maintenance of human energy homeostasis is regulated by a complex network. Peptides secreted from the gastrointestinal tract (GI) are signaling to the brain and other organs initiating or terminating food intake and energy expenditure. In the present study we investigated basal plasma levels of apelin, orexin-A, and leptin in morbid obese patients. In addition, we measured in a subgroup of these patients in the same individual orexin-A and leptin plasma levels one year after gastric banding surgery. METHODS: Basal plasma values were determined in obese patients (BMI=48+/-1 kg/m2n=32) after an overnight fast and compared to healthy, normal weighted (BMI=22+/-2 kg/m2n=12) controls. In addition, blood samples were collected in a subgroup of patients (BMI=48+/-1 kg/m2n=8) the day before surgery and 1 year after the operation. Apelin, orexin-A, and leptin levels were analysed using ELISAs. RESULTS: One year after the operation obese patients significantly lost weight (from 48+/-2 kg/m2 to 39+/-2 kg/m2; p<0,001). Apelin, orexin-A and leptin levels in obese patients were significantly higher compared to control individuals (736+/-50 pg/ml vs. 174+/-14 pg/ml, p<0.0001; 75.3+/-24.1 pg/ml vs. 0.8+/-0.4 pg/ml, p<0.0001; 79.0+/-2.4 ng/ml vs. 5.8+/-0.8 ng/ml, p<0.0001, respectively). Apelin and leptin plasma concentrations also correlated significantly with BMI (r=0.769, p<0.0001; r=0.778; p<0.0001, respectively), while orexin-A correlation was rather weak (r=0.335, p<0.03). No difference between pre- and post-operative orexin-A levels was observed, while leptin plasma levels significantly decreased from 45.1+/-5.4 ng/ml to 27.3+/-6.0 ng/ml (p=0.015). CONCLUSIONS: Apelin, orexin-A, and leptin plasma levels correlated positively with the BMI. One year after gastric banding with significant loss in BMI basal plasma levels of leptin decreased, while orexin-A remained unchanged.

Functions of orexins in peripheral tissues.

Orexin A (OXA) and orexin B were originally isolated as hypothalamic peptides regulating sleep, wakefulness and feeding. However, growing evidence suggests that orexins have major functions also in the peripheral tissues. Central orexigenic pathways originating from medulla activate the hypothalamus-pituitary axis and can influence the sympathetic tone. Orexins and their receptors are widely dispersed throughout the intestine, where orexin receptors are regulated by the nutritional status, affect insulin secretion and intestinal motility. Although the primary source of the peptide has not been elucidated, OXA is detected in plasma and its level varies in response to the metabolic state. In this review, we focus on the current knowledge on peripheral functions of orexins and discuss possible endocrine, paracrine and neurocrine roles.