Interaction of leptin and amylin in the long-term maintenance of weight loss in diet-induced obese rats.

Abstract

We have previously shown that combined amylin + leptin agonism elicits synergistic weight loss in diet-induced obese (DIO) rats. Here, we assessed the comparative efficacy of amylin, leptin, or amylin + leptin in the maintenance of amylin + leptin-mediated weight loss. DIO rats pretreated with the combination of rat amylin (50 microg/kg/day) and murine leptin (125 microg/kg/day) for 4 weeks were subsequently infused with either vehicle, amylin, leptin, or amylin + leptin for an additional 4 weeks. Food intake, body weight, body composition, plasma parameters, and the expression of key metabolic genes in liver and white adipose tissue (WAT) were assessed. Amylin + leptin treatment (weeks 0-4) reduced body weight to 87.5% of baseline. Rats subsequently maintained on vehicle or leptin regained all weight (to 104.2 and 101.2% of baseline, respectively), those maintained on amylin had partial weight regain (97.0%). By contrast, weight loss was largely maintained with continued amylin + leptin treatment (91.4%), associated with a 10% decrease in adiposity. Cumulative food intake (weeks 5-8) was reduced by amylin and amylin + leptin, but not by leptin alone. Amylin + leptin, but not amylin or leptin alone, reduced plasma triglycerides (by 55%), total cholesterol (by 19%), and insulin (by 57%) compared to vehicle. Amylin + leptin also reduced hepatic stearoyl-CoA desaturase-1 (Scd1) mRNA, and increased WAT mRNA levels of adiponectin, fatty acid synthase (Fasn), and lipoprotein lipase (Lpl). We conclude that, in DIO rats, maintenance of amylin + leptin-mediated weight loss requires continued treatment with both agonists, and is accompanied by sustained improvements in body composition, and indices of lipid metabolism and insulin sensitivity.

• Authors: James L Trevaskis, Chunli Lei, Joy E Koda, Christian Weyer, David G Parkes, Jonathan D Roth
• Journal: Obesity (Silver Spring, Md.) (Obesity (Silver Spring)) Vol. 18 Issue 1 Pg. 21-6 (Jan 2010) ISSN: 1930-739X [Electronic] United States
• PMID: 19543217 (Publication Type: Journal Article)

Chemical References

• Adiponectin
• Amyloid
• Appetite Depressants
• Insulin
• Islet Amyloid Polypeptide
• Leptin
• RNA, Messenger

Topics

• Adiponectin (blood)
• Adipose Tissue, White (metabolism)
• Amyloid (blood, pharmacology)
• Analysis of Variance
• Animals
• Appetite Depressants (pharmacology)
• Body Composition (drug effects)
• Body Weight (drug effects)
• Diet
• Drug Interactions
• Eating (drug effects)
• Gene Expression Profiling
• Insulin (blood)
• Islet Amyloid Polypeptide
• Leptin (blood, pharmacology)
• Liver (metabolism)
• Male
• Obesity (drug therapy, metabolism)
• RNA, Messenger (metabolism)
• Rats
• Weight Loss (drug effects)