Chronic PYY3-36 treatment promotes fat oxidation and ameliorates insulin resistance in C57BL6 mice.
PYY(3-36) is a gut-derived hormone acting on hypothalamic nuclei to inhibit food intake. We recently showed that PYY(3-36) acutely reinforces insulin action on glucose disposal in mice. We aimed to evaluate effects of PYY(3-36) on energy metabolism and the impact of chronic PYY(3-36) treatment on insulin sensitivity. Mice received a single injection of PYY(3-36) or were injected once daily for 7 days, and energy metabolism was subsequently measured in a metabolic cage. Furthermore, the effects of chronic PYY(3-36) administration (continuous and intermittent) on glucose turnover were determined during a hyperinsulinemic-euglycemic clamp. PYY(3-36) inhibited cumulative food intake for 30 min of refeeding after an overnight fast (0.29 +/- 0.04 vs. 0.56 +/- 0.12 g, P = 0.036) in an acute setting, but not after 7 days of daily dosing. Body weight, total energy expenditure, and physical activity were not affected by PYY(3-36). However, it significantly decreased the respiratory quotient. Both continuous and intermittent PYY(3-36) treatment significantly enhanced insulin-mediated whole body glucose disposal compared with vehicle treatment (81.2 +/- 6.2 vs. 77.1 +/- 5.2 vs. 63.4 +/- 5.5 micromol.min(-1).kg(-1), respectively). In particular, PYY(3-36) treatment increased glucose uptake in adipose tissue, whereas its impact on glucose disposal in muscle did not attain statistical significance. PYY(3-36) treatment shifts the balance of fuel use in favor of fatty acids and enhances insulin sensitivity in mice, where it particularly promotes insulin-mediated glucose disposal. Notably, these metabolic effects of PYY(3-36) remain unabated after chronic administration, in contrast to its anorexic effects.
van den Hoek
Anita M
AM
Leiden University Medical Center, Dept. of Endocrinology and Metabolic diseases, P. O. Box 9600, 2300 RC Leiden, The Netherlands.
Heijboer
Annemieke C
AC
Voshol
Peter J
PJ
Havekes
Louis M
LM
Romijn
Johannes A
JA
Corssmit
Eleonora P M
EP
Pijl
Hanno
H
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004734:Energy Metabolism / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007333:Insulin Resistance; D050356:Lipid Metabolism / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009928:Organ Specificity; D010101:Oxygen Consumption / Q000187:drug effects*; D010446:Peptide Fragments; D019894:Peptide YY / Q000494:pharmacology*
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D010446:Peptide Fragments; D019894:Peptide YY; C061785:peptide YY (3-36); D005947:Glucose