Antiobesity Effects of the β-Cell Hormone Amylin in Diet-Induced Obese Rats: Effects on Food Intake, Body Weight, Composition, Energy Expenditure, and Gene Expression

• Published in: Endocrinology (Philadelphia) 2006-12, Vol.147 (12), p.5855-5864
• Main Authors: Roth, Jonathan D, Hughes, Heather, Kendall, Eric, Baron, Alain D, Anderson, Christen M
• Format: Article
• Language: English
• Subjects: Adipose Tissue - metabolism; Agouti Signaling Protein; Amylin; Amyloid - pharmacology; Animals; Anti-Obesity Agents - pharmacology; Beta cells; Biological and medical sciences; Body Composition - drug effects; Body fat; Body weight; Body Weight - drug effects; Body weight gain; Body weight loss; Calorimetry, Indirect; Diet; Diet, Atherogenic; Eating - drug effects; Energy expenditure; Energy Metabolism - drug effects; Food composition; Food intake; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression - drug effects; Glycogen - analysis; Hypothalamic Hormones - metabolism; In Situ Hybridization; Intercellular Signaling Peptides and Proteins - genetics; Islet Amyloid Polypeptide; Liver - chemistry; Liver - metabolism; Liver Glycogen - analysis; Male; Medical sciences; Melanins - metabolism; Metabolic diseases; Metabolism; Mice; Muscle, Skeletal - chemistry; Neuropeptide Y; Neuropeptide Y - metabolism; Obesity; Obesity - blood; Obesity - etiology; Pituitary Hormones - metabolism; Pro-Opiomelanocortin - metabolism; Proopiomelanocortin; Quotients; Rats; Respiratory quotient; Thermogenesis; Thinness - blood; Triglycerides - analysis; Vertebrates: endocrinology; Weight control; Weight loss
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2006-0393

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 μg/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.