Lower leptin levels in mice selected for high voluntary wheel running

GIRARD*, I; REZENDE, EL; GARLAND, JR., T; Univ.of Wisconsin-Stevens Point; Univ.of Calif., Riverside; Univ.of Calif., Riverside: Lower leptin levels in mice selected for high voluntary wheel running

Selective breeding has produced 4 replicate lines of High-Runner (HR) mice that run about 2.7-times more revolutions/day as compared with 4 unselected Control (C) lines. Previous studies have shown that HR mice are smaller, have less body fat (by isotope dilution at 15 weeks of age), and lower relative retroperitoneal fat pad mass (males at 17 weeks of age). HR mice exhibit elevated corticosterone levels and increased insulin-stimulated glucose uptake by EDL muscle. We examined serum leptin, total body fat (by ether extraction), and organ masses in 8-week old females (n = 48). Mice had access to running wheels for 7 days at 7 weeks of age and were sacrificed after one additional week in home cages without wheels. Growth in body mass over the five weeks from weaning to sacrifice was 23% lower in HR than in C (P = 0.021). At sacrifice, total body dry mass was lower (P = 0.049) in HR (mean + SD; 6.60 + 1.16 g) than C (7.46 + 1.08 g), but absolute dry masses of the ventricles, liver, gut, and uterus plus ovaries did not differ (2-tailed P > 0.05). Percentage of the total dry mass as fat ranged from 13.7-47.1% in HR (28.9 + 10.2%) and 18.5-37.8% in C (30.1 + 5.8%) with no difference between linetypes. Serum leptin levels were significantly lower (P = 0.006) in HR (2.36 + 0.58 ng/ml) than C (3.80 + 1.57 ng/ml). Leptin was strongly positively correlated with both total body fat and mass change from weaning, but HR still had higher adjusted leptin levels (ANCOVA: body fat [%] P = 0.002; mass change P = 0.024; linetype P = 0.042). Wheel-running traits were not significant predictors of individual variation in leptin. HR mice show clear potential as a useful model for studying the causes and consequences of physiologically relevant variations in serum leptin. Supported by NSF IBN-0212567 to TG.

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