Antiobesity effects of the beta-cell hormone amylin in diet-induced obese rats: effects on food intake, body weight, composition, energy expenditure, and gene expression.
Effects of amylin and pair feeding (PF) on body weight and metabolic parameters were characterized in diet-induced obesity-prone rats. Peripherally administered rat amylin (300 microg/kg.d, 22d) reduced food intake and slowed weight gain: approximately 10% (P<0.05), similar to PF. Fat loss was 3-fold greater in amylin-treated rats vs. PF (P<0.05). Whereas PF decreased lean tissue (P<0.05 vs. vehicle controls; VEH), amylin did not. During wk 1, amylin and PF reduced 24-h respiratory quotient (mean+/-se, 0.82+/-0.0, 0.81+/-0.0, respectively; P<0.05) similar to VEH (0.84+/-0.01). Energy expenditure (EE mean+/-se) tended to be reduced by PF (5.67+/-0.1 kcal/h.kg) and maintained by amylin (5.86+/-0.1 kcal/h.kg) relative to VEH (5.77+/-0.0 kcal/h.kg). By wk 3, respiratory quotient no longer differed; however, EE increased with amylin treatment (5.74+/-0.09 kcal/.kg; P<0.05) relative to VEH (5.49+/-0.06) and PF (5.38+/-0.07 kcal/h.kg). Differences in EE, attributed to differences in lean mass, argued against specific amylin-induced thermogenesis. Weight loss in amylin and pair-fed rats was accompanied by similar increases arcuate neuropeptide Y mRNA (P<0.05). Amylin treatment, but not PF, increased proopiomelanocortin mRNA levels (P<0.05 vs. VEH). In a rodent model of obesity, amylin reduced body weight and body fat, with relative preservation of lean tissue, through anorexigenic and specific metabolic effects.
Roth
Jonathan D
JD
Amylin Pharmaceuticals, Inc., San Diego, California 92121, USA. jonathan.roth@amylin.com
Hughes
Heather
H
Kendall
Eric
E
Baron
Alain D
AD
Anderson
Christen M
CM
D000273:Adipose Tissue / Q000378:metabolism; D054366:Agouti Signaling Protein; D000682:Amyloid / Q000494:pharmacology*; D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology; D001823:Body Composition / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects*; D002153:Calorimetry, Indirect; D004036:Diet, Atherogenic; D004435:Eating / Q000187:drug effects*; D004734:Energy Metabolism / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects*; D006003:Glycogen / Q000032:analysis; D007028:Hypothalamic Hormones / Q000378:metabolism; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D058228:Islet Amyloid Polypeptide; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D008112:Liver Glycogen / Q000032:analysis; D008297:Male; D008543:Melanins / Q000378:metabolism; D051379:Mice; D018482:Muscle, Skeletal / Q000737:chemistry; D009478:Neuropeptide Y / Q000378:metabolism; D009765:Obesity / Q000097:blood / Q000209:etiology; D010907:Pituitary Hormones / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D051381:Rats; D013851:Thinness / Q000097:blood; D014280:Triglycerides / Q000032:analysis
D054366:Agouti Signaling Protein; D000682:Amyloid; D019440:Anti-Obesity Agents; D007028:Hypothalamic Hormones; D036341:Intercellular Signaling Peptides and Proteins; D058228:Islet Amyloid Polypeptide; D008112:Liver Glycogen; D008543:Melanins; D009478:Neuropeptide Y; D010907:Pituitary Hormones; D014280:Triglycerides; D011333:Pro-Opiomelanocortin; C019463:melanin-concentrating hormone; D006003:Glycogen