Endocrine Abstracts

The gastric hormone ghrelin stimulates feeding whereas the intestinal hormones peptide YY_3-36 (PYY_3-36) and oxyntomodulin inhibit feeding. In order to determine whether these gut hormones retain their effects in obesity, they were administered in vivo intraperitoneally to unanaesthetised lean and obese mice. Forty eight C57Bl/6 male mice were randomised to receive either low-fat diet (4.5% fat) or high fat diet (60% fat). After 16 weeks, mice fed on low-fat diet weighed 26.8±0.3grams and mice fed on high-fat diet weighed 39.1±0.8 grams. Ghrelin administration significantly stimulated feeding in lean freely-feeding mice (Energy intake 0-2 hours (kilocalories): saline 0.62±0.18, 100 nanomoles per kilogram ghrelin 1.24±0.14, 300 nanomoles per kilogram ghrelin 1.42±0.19). However no such stimulation was observed in the obese mice (Energy intake 0-2 hours (kilocalories): saline 0.55±0.08, 100 nanomoles per kilogram ghrelin 0.53±0.07, 300 nmol/kg ghrelin 0.60±0.11). In contrast, PYY_3-36 inhibited food intake in both lean and obese fasted mice (Lean energy intake 0-2 hours (kilocalories): saline 4.65±0.42, 10 nanomoles per kilogram PYY_3-36 2.72±0.29, 40 nanomoles per kilogram PYY_3-36 2.05±0.20) (Obese energy intake 0-2 hours (kilocalories): saline 2.09±0.33, 10 nanomoles per kilogram PYY_3-36 1.00±0.14, 40 nanomoles per kilogram PYY_3-36 0.99±0.20). Oxyntomodulin also inhibited food intake in lean and obese fasted mice. (Lean energy intake 0-2 hours (kilocalories): saline 5.23±0.44, 300 nanomoles per kilogram oxyntomodulin 3.85±0.25, 900 nanomoles per kilogram oxyntomodulin 3.86±0.22) (Obese energy intake 0-2 hours (kilocalories): saline 2.94±0.28, 300 nanomoles per kilogram oxyntomodulin 1.92±0.16, 900 nanomoles per kilogram oxyntomodulin 1.87±0.20). Thus the stimulatory feeding effect of ghrelin appears to be lost in dietary-induced obesity in the mouse whereas the inhibitory effects of PYY_3-36 and oxyntomodulin are retained. These findings suggest that stimulation of the inhibitory gut hormones could prove more effective in the treatment of obesity than blockade of the stimulatory gut hormone, ghrelin.