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1 Biomedical Sciences, Creighton University, Omaha, Nebraska, USA
2 Research Service, Department of Veterans Affairs - Nebraska Western Iowa Health Care System, Omaha, Nebraska, USA
3 CURE: Digestive Diseases Research Center, Department of Veterans Affairs - Greater Los Angeles Healthcare System, Los Angeles, California, USA; Digestive Diseases Division, David Geffen UCLA School of Medicine, Los Angeles, California, USA
4 Research Service, Department of Veterans Affairs - Nebraska Western Iowa Health Care System, Omaha, Nebraska, USA; Biomedical Sciences, Creighton University, Omaha, Nebraska, USA
* To whom correspondence should be addressed. E-mail: roger.reidelberger{at}med.va.gov.
The gut hormone peptide YY(3-36) [PYY(3-36)] decreases food intake when administered by intravenous infusion to lean and obese humans, and rats. Whether chronic administration of PYY(3-36) produces a sustained reduction in food intake and adiposity is the subject of intense debate. Batterham et al. (7) first reported that PYY(3-36) reduces food intake and weight gain in rats when injected into the peritoneal cavity twice daily for 7 days. Numerous laboratories have failed to confirm that daily injections of PYY(3-36) decrease body weight. Continuous subcutaneous administration of PYY(3-36) by osmotic minipump has been reported to reduce daily food intake in rodents, but only during the first 3-4 days of administration. Here we show the effects of different daily patterns of intravenous infusion of PYY(3-36) on food intake, body weight, and adiposity in rats tethered via infusion swivels to computer-controlled pumps. Measurement of food bowl weight, recorded by computer every 20 seconds, permitted daily assessment of the instantaneous effects of PYY(3-36) administration on food intake and meal patterns. One-hour intravenous infusions of PYY(3-36) at 30 pmol/kg/min every other hour for 10 days produced a sustained reduction in daily food intake of about 20%, and decreased body weight and adiposity by 7 and 35%, respectively. Thus, dosage pattern is critical for producing a sustained effect of PYY(3-36) on food intake and adiposity.
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