Plasma obestatin levels are lower in obese and post-gastrectomy subjects, but do not change in response to a meal

Abstract

Objective: To investigate a potential role for obestatin in humans by examining response to a fixed energy meal. Context: A new anorectic peptide hormone, obestatin has recently been isolated from rat stomach. The significance of this peptide in humans is unknown. Study design: Case-control study. Setting: Hospital-based study. Patients: Nine healthy controls, nine morbidly obese subjects and eight post-gastrectomy subjects. Intervention: Subjects attended after an overnight fast and were given a fixed energy meal (1550 kJ). Main outcome measure: The response of obestatin to a meal in the different groups. Results: Fasting obestatin was significantly lower in obese subjects as compared to lean subjects (27.874 vs 17.272 pg/ml, P ¼ 0.03). Obestatin was also decreased in gastrectomy subjects but this did not reach statistical significance (27.874 vs 21.973 pg/ml, P ¼ 0.3). Obestatin did not change significantly from baseline in response to the meal. Lean and obese subjects had a similar obestatin/ghrelin ratio (0.0470.003 vs 0.0570.009, P ¼ 0.32), but this was higher in the gastrectomy group (0.0470.003 vs 0.170.01, Po0.001). Conclusions: Obestatin does not vary significantly with a fixed energy meal, but is significantly lower in morbidly obese subjects as compared to lean subjects supporting a possible role for obestatin in long-term body weight regulation. Obestatin tended to be lower in gastrectomy subjects and their obestatin/ghrelin ratio differed from healthy controls. Hence, the expression of obestatin is altered following gastrectomy, suggesting other sites outside the stomach may also secrete obestatin.

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

“…The plasma des-acyl ghrelin concentration significantly decreased after a meal, while the plasma obestatin concentration did not change. Human plasma obestatin concentration did not change even after intake of a 1550 kcal meal (Huda et al 2008). Thus, obestatin secretion does not appear to be influenced by dietary nutrients.…”

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

“…High levels of GPR39 mRNA were found abundantly in the amygdala, the hippocampus, and the auditory cortex but not in the hypothalamus Jackson et al, 2006). Plasma obestatin levels were lower in obese subjects and those who had undergone gastrectomy (Huda et al, 2008). 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).…”

“…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 .…”

Diabetes, Ghrelin And Related Peptides: From Pathophysiology To Vasculopathy

“…As a result, the effects of obestatin on food intake may be secondary to an action of the peptide to inhibit water drinking, a phenomenon known as dehydration anorexic effect [67]. Obestatin levels do not vary with a fixed energy meal, but are lower in obese subjects supporting a possible role for obestatin in long-term body weight regulation [115]. The effects of ghrelin, des-acyl ghrelin and obestatin in metabolism regulation are summarized in Table 1.…”