Intravenous Infusion of Peptide YY(3–36) Potently Inhibits Food Intake in Rats

Abstract

Peptide YY (3-36) [PYY (3-36)] is postulated to act as a hormonal signal from the gut to the brain to inhibit food intake and gastric emptying. A mixed-nutrient meal produces a prolonged 2-3 h increase in plasma levels of both PYY (3-36) and PYY (1-36). We determined the dose-dependent effects of 3-h iv infusions of PYY (3-36) and PYY (1-36) (0.5-50 pmol.kg(-1).min(-1)) at dark onset on food intake in non-food-deprived rats. PYY (3-36) dose-dependently inhibited food intake: the minimal effective dose was 5 pmol.kg(-1).min(-1); the estimated potency (mean effective dose) and efficacy (maximal percent inhibition) were 15 pmol.kg(-1).min(-1) (2.6 nmol/kg) and 47%, respectively. PYY (1-36) was an order of magnitude less potent than PYY (3-36). Similar total doses of PYY (3-36) (0.9-30 nmol/kg) infused during the 15-min period just before dark onset also dose-dependently inhibited food intake, albeit with a lower potency and efficacy. Other experiments showed that PYY (3-36) inhibited food intake in sham-feeding rats and was more effective in reducing intake of a mixed-nutrient liquid diet than 15% aqueous sucrose. We conclude that: 1) iv infusions of PYY (3-36), which are more likely than ip injections to mimic postprandial increases in plasma PYY (3-36), potently inhibit food intake in a dose-dependent manner; 2) PYY (1-36) is an order of magnitude less potent than PYY (3-36); and 3) PYY (3-36) can inhibit food intake independently of its action to inhibit gastric emptying. It remains to be determined whether iv doses of PYY (3-36) that reproduce postprandial increases in plasma PYY (3-36) are sufficient to inhibit food intake.

Single nucleotide polymorphisms in the neuropeptide Y2 receptor (NPY2R) gene and association with severe obesity in French white subjects

“…Over the last few years much emphasis has been placed on the role of PYY, PPY and NPY2R in relation to obesity [6,12,16,22,28,33] in both humans and animal models. From the literature it has been demonstrated that NPY2R is a crucial receptor in appetite regulation.…”

“…Batterham et al provided the first evidence that PYY is a mediator of postprandial satiety in rodents [6] and humans [12] through actions at the arcuate nucleus via NPY2 receptor (NPY2R). Since then many studies have established the role of PYY in decreasing food intake in both animals [13][14][15][16][17][18] and humans [19][20][21]. However, contradictory evidence has also been presented, suggesting that PYY does not decrease food intake in rodents, further questioning its role as a potential anti-obesity drug target [22,23].…”

PYY transgenic mice are protected against diet-induced and genetic obesity

“…Recent studies have demonstrated acute affects of PYY1-36 and PYY3-36 in inhibiting food intake in animals and in man (Adams et al, 2004, Batterham et al, 2002, Challis et al, 2003, Chelikani et al, 2004, Chelikani et al, 2005, Halatchev et al, 2004and Riediger et al, 2004. It is thought that after a meal, PYY3-36, the main form of PYY circulating postprandially, acts on the arcuate nucleus of the hypothalamus.…”

Sir David Cuthbertson Medal Lecture Bariatric surgery as a model to study appetite control

“…The major form of circulating PYY is the N-terminally truncated PYY3-36, which has high affinity for the Y2 receptor and a lesser affinity for Y1 and Y5 receptors (71) . Although initially controversial, peripheral administration of PYY3-36 at physiological doses has now been accepted to reduce food intake in rodents, primates and human subjects in the short term (72)(73)(74)(75) . PYY-knock-out mice are characterized by dysregulation of energy homeostasis (76) .…”