A dwarf transgenic mouse (DTM) line has been established in which mice express relatively high levels of a mutated bovine (b) GH gene. This bGH analog binds to mouse liver membrane preparations with an affinity similar to that of wild-type bGH. The mean growth ratio of these mice is approximately 0.7 relative to that of their nontransgenic littermates. Serum insulin-like growth factor-I (IGF-I) levels of DTM were found to be approximately half those in nontransgenic littermates. Liver GH receptor levels were up-regulated in DTM or wild-type bGH transgenic mice. Pituitary GH levels were negatively correlated with serum IGF-I concentrations. Wild-type bGH transgenic mice contain relatively high serum IGF-I and low pituitary GH levels, whereas DTM possess low serum IGF-I and high pituitary GH levels. The decrease in serum IGF-I resulting from the interaction between the bGH analog, the endogenous mouse GH, and GH receptor(s) apparently leads to a dwarf phenotype. These data suggest that this bGH analog has uncoupled GH ligand-receptor binding from IGF-I production and acts as a functional antagonist to the action of endogenous mGH.

Alterations in body composition and nutritional status are common in humans with heart failure and are related, in part, to increases in cytokine concentrations. Cytokines have not been studied previously in dogs with naturally occurring cardiac disease nor has fish oil administration been used in this population to decrease cytokine production. The purposes of this study were to characterize nutritional and cytokine alterations in dogs with heart failure and to test the ability of fish oil to reduce cytokines and improve clinical outcome. Body composition, insulinlike growth factor-1, fatty acids, and cytokines were measured in 28 dogs with heart failure and in 5 healthy controls. Dogs with heart failure then were randomized to receive either fish oil or placebo for 8 weeks. All parameters were measured again at the end of the study period. At baseline, 54% of dogs with heart failure were cachectic and the severity of cachexia correlated with circulating tumor necrosis factor-alpha concentrations (P = .05). Cytokine concentrations at baseline, however, were not significantly increased in dogs with heart failure compared to controls. Baseline plasma arachidonic acid (P = .02), eicosapentaenoic acid (P = .03), and docosahexaenoic acid (P = .004) concentrations were lower in dogs with heart failure than in controls. Fish oil supplementation decreased interleukin-1 beta (IL-1) concentrations (P = .02) and improved cachexia (P = .01) compared to the placebo group. The mean caloric intake of the heart failure dogs as a group was below the maintenance energy requirement (P < .001), but no difference was found in food intake between the fish oil and placebo groups. Insulinlike growth factor-1 concentrations (P = .01) and reductions in circulating IL-1 concentrations over the study period (P = .02) correlated with survival. These data demonstrate that canine heart failure is associated with cachexia, alterations in fatty acids, and reduced caloric intake. Fish oil supplementation decreased IL-1 concentrations and improved cachexia. In addition, reductions in IL-1 predicted survival, suggesting that anticytokine strategies may benefit patients with heart failure.

Effects of three dietary lysine (protein) concentrations during lactation on metabolic state, protein metabolism, reproductive hormones, and performance were investigated in 36 primiparous sows. Sows were assigned randomly to one of three diets containing .4% (low lysine, LL), 1.0% (medium lysine, ML), or 1.6% (high lysine, HL) total lysine from intact protein sources. All diets contained 2.1 Mcal NE/kg and exceeded the recommended requirements for all other nutrients. Actual lysine intakes over an 18-d lactation were 16, 36, and 56 g/d for sows fed LL, ML, and HL, respectively. Fractional breakdown rate of muscle was determined on d 4 and 15 of lactation by using a three-compartment kinetic model of 3-methylhistidine metabolism. Increasing lysine intake during lactation did not affect fractional breakdown rate of muscle on d 4 of lactation but decreased it on d 15 (P < .05). Sows fed LL had a reduced number of LH pulses on d 12 and 18 (P < .05) and reduced serum estradiol (E2) concentration on d 18 of lactation compared with sows fed ML and HL treatments. However, LH pulses and E2 concentrations were similar between ML and HL treatments (P > .35). Increasing lysine intake increased serum urea nitrogen (SUN) and postprandial insulin concentrations (P < .05) during lactation but had no effect on plasma glucose concentrations (P > .20). Sows fed HL had greater serum IGF-I on d 6 and 18 than sows fed ML (P < .05). Number of LH peaks was correlated with serum insulin concentration 25 min after feeding on d 6 and 18 (r = .31 to .41; P < .1) and pre- (r = .33 to .46) and postprandial (r = .30 to .58) SUN concentrations (P < .05) during different stages of lactation. Results indicate that, compared with medium lysine intake, low lysine intake increased muscle protein degradation and decreased concentrations of insulin, SUN, and estradiol and LH pulsatility. In contrast, high lysine (protein) intake increased SUN, insulin, and IGF-I, but did not increase secretion of estradiol and LH compared with medium lysine intake. Furthermore, nutritional impacts on reproduction may be mediated in part through associated effects on circulating insulin concentration.

Muscle satellite cells were isolated from seven yearling steers implanted for 31 d with a combined implant that contained 120 mg of trenbolone acetate (TBA) and 24 mg of estradiol (E2) and from seven nonimplanted, control steers. Implanted steers had a 28% greater ADG and a 23% greater feed efficiency than did nonimplanted steers. Implanted steers had increased (P<.001) circulating IGF-I concentrations on d 6, 14, and 31 after implantation, and circulating IGF-I concentrations in control steers remained constant or decreased (P<.05) at these times. Maximum fusion percentage was greater (P< .005) in satellite cell cultures isolated from implanted steers (ISC cultures) than in satellite cell cultures isolated from control steers (NSC cultures) (72.8% vs 54.8%, respectively). Satellite cell cultures isolated from implanted steers (ISC cultures) also contained a greater (P<.001) number of myotube nuclei than did NSC cultures (7,998 nuclei/cm2 vs 5,150 nuclei/cm2, respectively). After 72 h in culture, the number of cells (corrected for plating density) was 43% greater (P<.05) in ISC cultures than in NSC cultures. [3H]Thymidine incorporation rates per 10(5) cells at 24 and 34 h after plating were greater (P<.05) in ISC cultures than in NSC cultures; however, incorporation rates did not differ at 72 h. These data indicate that TBA + E2 implantation may result in an in vivo activation of muscle satellite cell proliferation that can be detected in cell culture. This activation may play an important role in TBA + E2-enhanced muscle growth.