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Effects of PYY_1–36 and PYY_3–36 on appetite, energy intake, energy expenditure, glucose and fat metabolism in obese and lean subjects

¹Department of Human Nutrition, Centre for Advanced Food Studies, Faculty of Life Sciences, University of Copenhagen, Frederiksberg; and ²Department of Medical Physiology, The Panum Institute, University of Copenhagen, Copenhagen, Denmark

Submitted 25 August 2006 ; accepted in final form 4 December 2006

Peptide YY (PYY)_3–36 has been shown to produce dramatic reductions in energy intake (EI), but no human data exist regarding energy expenditure (EE), glucose and fat metabolism. Nothing is known regarding PYY1-36. To compare effects of PYY_1–36 and PYY_3–36 on appetite, EI, EE, insulin, glucose and free fatty acids (FFA) concentrations, 12 lean and 12 obese males participated in a blinded, randomized, crossover study with 90-min infusions of saline, 0.8 pmol·kg^–1·min^–1 PYY_1–36 and PYY_3–36. Only four participants completed PYY_3–36 infusions because of nausea. Subsequently, six lean and eight obese participants completed 0.2 pmol·kg^–1·min^–1 PYY_3–36 and 1.6 pmol·kg^–1·min^–1 PYY_1–36 infusions. PYY_3–36 at 0.8 pmol·kg^–1·min^–1 produced reduced EI, lower ratings of well-being, increases in FFA, postprandial glucose (only 0.8 pmol·kg^–1·min^–1 PYY_3–36) and insulin concentrations, as well as heart rate and EE (only 0.8 pmol·kg^–1·min^–1 PYY_3–36). PYY_1–36 at 1.6 pmol·kg^–1·min^–1 produced increased heart rate and postprandial insulin response. Ratings of appetite were opposite with infusions of 0.8 and 1.6 pmol·kg^–1·min^–1 PYY_1–36 and seemed to depend on subjects being lean or obese. PYY_3–36 caused increased thermogenesis, lipolysis, postprandial insulin and glucose responses, suggestive of increased sympathoadrenal activity. PYY_1–36 had no effect on EI and no clear effects on appetite but resulted in increased heart rate and postprandial insulin response. However, highest tolerable dose of PYY_1–36 was probably not reached in the present study.

Peptide YY; free fatty acids; insulin sensitivity; arcuate nucleus; neuropeptide Y receptors

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