Characterization of obestatin in rat and human stomach and plasma, and its lack of acute effect on feeding behavior in rodents

Abstract

Obestatin is a 23-amino acid peptide, initially isolated from rat stomach as an endogenous ligand for the orphan G-proteincoupled receptor. Obestatin is derived from proteolytic cleavage of a 117-amino acid precursor, preproghrelin. Ghrelin increases food intake, body weight, and gastric emptying, whereas obestatin has the opposite effects. In this study, we characterized obestatin in both rat and human stomach, and investigated the peptide's effect on feeding behavior. Using reversed-phase high-performance liquid chromatography coupled with RIAs specific for rat and human obestatin, we detected a very small amount of obestatin, compared with ghrelin, in the gastric fundi. The ratios of obestatin to ghrelin are 0 . 0039 and 1 . 94% respectively in the rat and human gastric fundi. In humans, plasma obestatin accounted for 5 . 21% of the ghrelin concentration, whereas it was undetectable in rat plasma. Plasma ghrelin concentration decreased after a meal in normal subjects, whereas obestatin concentration did not change. When administered centrally or peripherally, obestatin did not suppress food intake in either free-feeding or fasted rodents. Administration of obestatin did not antagonize ghrelin-induced feeding. These findings indicate that obestatin is present at very low levels compared with ghrelin in both rat and human, and has no acute effect on feeding behavior.

Ghrelin Gene Products and the Regulation of Food Intake and Gut Motility

“…However, recent studies indicate that obestatin is not the endogenous cognate ligand for GPR39 (Lauwers et al, 2006;Holst et al, 2007;Chartrel et al, 2007), whereas a more recent study demonstrated that obestatin was a metabolic hormone capable of binding to GPR39 and, in turn, of regulating the diverse biological functions of gastrointestinal and adipose tissues (Zhang et al, 2008a). The plasma obestatin concentration did not change after a 450-kcal (Mondal et al, 2008) or even a 1550-kcal (Huda et al, 2008) meal in humans, identifying that obestatin secretion is not influenced by dietary nutrients. The effects of obestatin on food intake 438 remain controversial .…”

“…Fasting induced the elevation of des-acyl ghrelin, the second ghrelin gene product, in mice (Kirchner et al, 2009), rats (Seoane et al, 2007a), and humans Mondal et al, 2008), whereas feeding suppressed it (Seoane et al, 2007a;Liu et al, 2008;Mondal et al, 2008;Kirchner et al, 2009). Des-acyl ghrelin has been demonstrated to decrease food intake in mice (Asakawa et al, 2005) and rats (Chen et al, 2005a,b) centrally and peripherally in the fasted state.…”

“…The effects of obestatin on food intake 438 remain controversial . Obestatin has been demonstrated to inhibit food intake in rodents (Zhang et al, 2005;Bresciani et al, 2006;Sibilia et al, 2006;Chartrel et al, 2007;Zizzari et al, 2007;Carlini et al, 2007;Green et al, 2007), whereas several research groups fail to show this anorexigenic effect (Seoane et al, 2006;Gourcerol et al, 2007;Nogueiras et al, 2007;Yamamoto et al, 2007;De Smet et al, 2007;Annemie et al, 2009;Kobelt et al, 2008;Mondal et al, 2008;Unniappan et al, 2008). Obestatin had no effect on body weight (Sibilia et al, 2006;Unniappan et al, 2008).…”

Biological effects of obestatin

“…In addition, exogenous obestatin inhibited the ghrelin orexigenic effect that was evident in fed mice [20]. On the other hand, many reports have stated that obestatin did not show any effect on food intake in mice or rats [24,32,34,37,[74][75][76]. Obestatin treatment did not modify either daily calorie intake or body-weight gain in highly palatable cafeteria-style diet-fed rats [73].…”

“…Basal obestatin levels in females were higher compared to males [23]. The half-life of obestatin was only 2 min [24]. However, Morash et al recently reported that they did not detect fasting-induced changes in tissue obestatin expression or plasma obestatin level [25].…”