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Adipose tissue secretes leptin, which interacts with receptors in the hypothalamus. In rodent models of obesity, leptin increases metabolism and decreases food intake, which helps to maintain normal body composition. Accurate and precise methods to quantitate circulating leptin concentrations are needed for physiological studies. We developed an RIA to measure leptin in rat plasma, serum, or adipocyte culture fluids. The working range of the assay, defined by the detection limit and the highest calibrator, was 0.5–50 μg/L. Recovery of 1.6–11.6 μg/L leptin added to serum was 92–103%. The rat leptin RIA correlated well with a previously developed mouse RIA when rat plasma was assayed with both methods (r = 0.94), but the mouse leptin assay underestimated rat leptin in plasma. Within- and between-run CVs were 2.4% to 5.7%. Plasma leptin concentrations correlated directly with percentage of body fat, and correlation improved when the results were separated by gender (r = 0.796, P

The loss of muscle strength with age has been studied from the perspective of a decline in muscle mass and neuromuscular junction (NMJ) stability. A third potential factor is force transmission. The purpose of this study was to determine the changes in the force transfer apparatus within aging muscle and the impact on membrane integrity and NMJ stability. We measured an age-related loss of dystrophin protein that was greatest in the flexor muscles. The loss of dystrophin protein occurred despite a twofold increase in dystrophin mRNA. Importantly, this disparity could be explained by the four- to fivefold upregulation of the dystromir miR-31. To compensate for the loss of dystrophin protein, aged muscle contained increased α-sarcoglycan, syntrophin, sarcospan, laminin, β1-integrin, desmuslin, and the Z-line proteins α-actinin and desmin. In spite of the adaptive increase in other force transfer proteins, over the 48 hours following lengthening contractions, the old muscles showed more signs of impaired membrane integrity (fourfold increase in immunoglobulin G-positive fibers and 70% greater dysferlin mRNA) and NMJ instability (14- to 96-fold increases in Runx1, AchRδ, and myogenin mRNA). Overall, these data suggest that age-dependent alterations in dystrophin leave the muscle membrane and NMJ more susceptible to contraction-induced damage even before changes in muscle mass are obvious.

The tumor-promoting activity of two beta-adrenoreceptor blocking agents, propranolol and atenolol, was tested in a two-stage protocol of hepatocarcinogenesis in male and female Fischer 344 rats. Propranolol is a lipophilic non-selective beta-blocker mainly eliminated via the liver; atenolol is a hydrophilic beta 1-selective blocking agent, mainly eliminated via the kidney. Animals were initiated with a single dose of diethylnitrosamine (DEN, 200 mg/kg, i.p.) and, after 17 days of recovery, were continuously treated with propranolol (75-100 mg/kg) or atenolol (300 mg/kg) by gavage for up to 21 months. Rats given phenobarbital (0.05% in the diet) were used as positive controls. After 2, 4 and 8 months of promotion, preneoplastic lesions were quantified by staining sections of liver for gamma-glutamyltranspeptidase (GGT). In non-initiated rats, neither propranolol nor atenolol influenced the development of spontaneous preneoplastic or neoplastic liver lesions. The results obtained in DEN-initiated rats given propranolol cannot be unequivocally interpreted. In the male, propranolol seemed to be ineffective. In the female, there was weak enhancement of DEN-induced GGT foci at 4 and 8 months and of neoplastic lesions thereafter. However, there was great interindividual variability in focus and tumor yields. Unfortunately, due to the high incidence of liver tumors in rats given DEN alone and the small number of propranolol-treated rats that survived until the end of the experiment, no definite conclusion can be drawn about the modifying potential of this beta-blocker on liver carcinogenesis. There was no evidence of liver tumor promotion in DEN-initiated rats of either sex given atenolol.