Effects of a potent melanocortin agonist on the diabetic/obese phenotype in yellow mice.
OBJECTIVE
To test the hypothesis that a melanocortin agonist can reverse obesity and insulin resistance in mice overexpressing the agouti protein. EXPERIMENTAL MODEL: Mice overexpressing the agouti protein either by transgene introduction (beta-actin promotor) or by mutation (Ay).


METHODS
NDPMSH was tested for pharmacokinetic suitability. NDPMSH at various doses was administered subcutaneously twice a day for 2-3 weeks.


METHODS
Fur pigmentation, various fatness parameters (core temperature, fat pad weight and body weight), blood glucose and hormones, fatty acid synthase measurement.


RESULTS
NDPMSH caused fur pigmentation and core temperature changes, but failed to affect any metabolic parameters in agouti-dependent manner.


CONCLUSIONS
NDPMSH, as a representation melanocortin agonist, does not compete with agouti in reversing agouti-dependent metabolic effects. This suggests that 1) agouti works via a receptor other than a melanocortin receptor to mediate its metabolic effects, 2) agouti-dependent metabolic effects are mediated through melanocortin receptors but not via antagonism of these receptors, or 3) NDPMSH is pharmacodynamically an inappropriate molecule for these types of studies.
Zemel
M B
MB
Department of Nutrition, University of Tennessee, Knoxville, USA.
Moore
J W
JW
Moustaid
N
N
Kim
J H
JH
Nichols
J S
JS
Blanchard
S G
SG
Parks
D J
DJ
Harris
C
C
Lee
F W
FW
Grizzle
M
M
James
M
M
Wilkison
W O
WO
D054366:Agouti Signaling Protein; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003920:Diabetes Mellitus / Q000188:drug therapy*; D006200:Hair Color / Q000187:drug effects; D007333:Insulin Resistance; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D008822:Mice, Transgenic; D009765:Obesity; D010641:Phenotype; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D011979:Receptors, Pituitary Hormone / Q000378:metabolism; D015430:Weight Gain / Q000187:drug effects; D000521:alpha-MSH / Q000819:agonists* / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use
D054366:Agouti Signaling Protein; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D011979:Receptors, Pituitary Hormone; C515183:a protein, mouse; D000521:alpha-MSH; C027756:MSH, 4-Nle-7-Phe-alpha-; C029446:MSH receptor