In this study, we found that the level of plasma obestatin was significantly higher in COPD patients than in the control group. Significant correlation was found between the level of plasma obestatin and the systemic inflammatory markers: CRP and TNF-α. No significant correlation was found between the level of plasma obestatin and nutrition status parameters such as BMI, % body fat, FFM, waist circumference, hip circumference, waist hip ratio, cholesterol, triglyceride, glucose, or insulin. No significant correlation was found between the level of plasma obestatin and lung function.

Obestatin is a 23-amino acid peptide hormone released from the cells lining the stomach. Studies in humans have shown that plasma obestatin levels are significantly lower in obese subjects as compared to lean controls, indicating a role for obestatin in body weight regulation. Gao et al. [16] found the number of obestatin-positive cells in gastric body mucosa was significantly lower in overweight and obese patients than in healthy controls with normal weight. The concentration of plasma obestatin was also decreased in overweight and obese patients and positively correlated with the number of obestatin-positive cells in the gastric body mucosa. The authors suggested that overweight and obese subjects have a reduction in the number of obestatin-positive cells in the gastric body mucosa. In our study, the level of circulating obestatin was found to be higher in COPD patients with malnutrition than in the healthy control group. The exact mechanism of obestatin increase in COPD with malnutrition is not clear because the regulation of the expression of obestatin remains unknown at present. It was reported that the production of ghrelin, an adipokine derived from the same gene as obestatin, was regulated by other adipokines, (such as leptin) inflammation, or diet [17, 18]. Zhang et al. [7] reported that although fasting led to higher level of ghrelin, the serum level of obestatin was constant after fasting in rats. These results suggested that although they are encoded by the same gene, the production of ghrelin and obestatin is regulated by different factors. Obestatin was found to be positively correlated with IL-6 in the BD patients, and with the level of TNF-α in the control group. It was also correlated with CRP and TNF-α in COPD. Increased obestatin may then be the result of inflammation in COPD, a disease with chronic systemic inflammation.

Obestatin was reported to suppress food intake, inhibit jejunal contraction, and decrease weight gain [7]. Although the level of plasma obestatin was higher in COPD patients compared with age-matched controls, no significant correlation was found between obestatin and BMI, % body fat, FFM, waist circumference, hip circumference, or waist hip ration in COPD. Although Xin et al. [13] reported that the level of obestatin was negatively correlated with BMI in chronic heart failure (CHF) patients, plasma obestatin did not correlate with BMI or other nutrition parameters in COPD in this study. Other studies also found that obestatin was inversely correlated with BMI in chronic kidney disease and hemodialysis patients. Gao et al. [16] reported that negative correlation was found between circulating obestatin levels and BMI in healthy subjects, but not in patients with chronic atrophic gastritis. This result suggests that obestatin expression in some diseases may be different from healthy patients. Zhang et al. [7] found that obestatin suppressed food intake in fasting mice and spontaneously reduced weight gain at large doses in lean mice. Another research demonstrated that obestatin exerted no effect on food intake and body weight in rats [19]. Other authors [14] found that Roux-en-Y gastric bypass (RYGB) surgery and/or the weight loss resulted in the decrease of ghrelin level but had no effect on obestatin levels. Thus, the role of obestatin in energy metabolism still remains uncertain.

Although the level of obestatin did not correlate with COPD nutritional status, correlation analysis showed that the level of plasma obestatin did positively correlate with CRP and TNF-α in COPD patients. It was reported that ghrelin inhibited various inflammation processes in arthritic rats, acute lung injury, and other inflammation diseases [20, 21]. Since obestatin is derived from the same gene which also encodes ghrelin, it may play a role in systemic inflammation in COPD. Until now, only a few studies have investigated the role of obestatin in inflammation. Kellokoski et al. [10] reported that obestatin did not influence the adhesion of monocytes. Although obestatin treatment did not change the expression of either intercellular adhesion molecule-1 (ICAM-1) or monocyte chemoattractant protein-1 (MCP-1), obestatin treatment together with TNF-α suppressed the expression of VCAM-1, but did not alter ICAM-1 or MCP-1 expressions. As TNF-α and other pro-inflammatory cytokines increase in COPD, whether obestatin inhibits systemic inflammation by suppressing the expression of VCAM and other adhesion molecules requires further investigation. Koca et al. [22] reported that no positive correlation was found between the level of obestatin and some inflammatory markers in two chronic inflammatory diseases -RA and BD. This is different from our results. In their study, medications affecting the immune system were administrated to RA and BD patients but not to the control group. This may have affected the level of obestatin in their RA and BD groups. In contrast to our study in which no medication was administered to the COPD group or the control group, Xin et al. [13] reported that the level of obestatin was higher in CHF patients with cachexia compared with non-cachexia and normal controls. They also found that the level of plasma obestatin had a negative correlation with BMI. Since CHF is regarded as a disease with chronic systemic inflammation [23, 24], the different levels of plasma obestatin in CHF patients and their negative correlation with BMI may be the result of the systemic inflammation of this disease.