Gastric Distress for Obestatin

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Science  24 Nov 2006:
Vol. 314, Issue 5803, pp. 1218
DOI: 10.1126/science.314.5803.1218b

In a developed world suffering an obesity epidemic, new reports of molecules that regulate appetite and body weight inevitably attract broad interest, and the secreted peptide obestatin (Zhang et al., Research Articles, p. 996, 11 November 2005) was no exception. Derived from the same precursor as ghrelin (a peptide that promotes food intake and obesity in rodent models), obestatin was shown to have activities that oppose the effects of ghrelin: It suppressed food intake, delayed gastric emptying, and decreased body weight gain in rodents. These intriguing effects were mediated by its interaction with a G-protein-coupled receptor called GPR39.

Subsequent experiments in other laboratories suggest that obestatin may be regulating energy balance in a manner distinct from that originally proposed and/or that its effect on food intake is subtle. Moechars et al. found that mice genetically deficient in GPR39, the putative receptor for obestatin, gain weight more readily than their wild-type littermates, but they attributed this to the inhibitory effects of GPR39 on gastrointestinal motility rather than appetite, as food intake was similar for the mutant and wild-type mice. Nogueiras et al. injected rats with obestatin obtained from three different suppliers and found that obestatin had no effect on food intake, body weight, or other physiological parameters involved in energy balance. Importantly, neither group was able to detect expression of the GPR39 gene in the hypothalamus, the region of the brain targeted by most hormones associated with appetite control. — PAK

Gastroenterology 131, 1131 (2006); Endocrinology 10.1210/en.2006-0915 (2006).

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