Effect of a short-term fast on intestinal disaccharidase activity and villus morphology of piglets suckling insulin-like growth factor-I transgenic sows.

The objectives of this study were to use transgenic sows that overexpress IGF-I in milk to investigate the effect of a short-term fast on piglet intestinal morphology and disaccharidase activity and to determine how milk-borne IGF-I influences the response to fasting. After farrowing, litters were normalized to 10 piglets. On d 6, piglets (n = 30) suckling IGF-I transgenic (TG) sows and piglets (n = 30) suckling nontransgenic sows (control) were assigned randomly to three treatments: fed piglets (0 h), which remained with the sow until euthanized on d 7, or fasted piglets, which were removed from the sow at either 6 or 12 h before euthanasia on d 7. Serum IGF-I and IGFBP, intestinal weight and length, jejunal protein and DNA content, disaccharidase activity, and villus morphology were measured. Fasting for 12 h resulted in a negative weight change between d 6 and 7 (quadratic response to fasting; P < 0.001). Piglets suckling TG sows tended to have greater intestinal length (P = 0.068), but no effect of IGF-I overexpression was noted for intestinal weight. Fasting, however, resulted in linear (P < 0.001) and quadratic (P = 0.002) decreases in intestinal weight. Serum IGF-I did not differ between control and TG sows, but decreased linearly (P = 0.003) with fasting. Serum IGFBP-4 decreased (linear and quadratic; P < or = 0.02) with fasting, whereas IGFBP-1 increased quadratically (P < 0.001) with fasting. Jejunal villus height, width, and crypt depth were all increased with fasting (linear and quadratic; P < 0.04). Disaccharidase activity was not affected by fed state; however, piglets suckling TG sows had greater jejunal lactase-phlorhizin hydrolase (P < 0.01) and sucrase-isomaltase (P = 0.02) activities than control piglets. In summary, intestinal weight, villus morphology, serum IGF-I, serum IGFBP-1 and -4, and piglet BW change were altered (P < or = 0.02) in response to fasting. Thus, the duration of food deprivation before euthanization should be considered when designing experiments to assess intestinal development or the IGF axis, as the magnitude of differences between the fed and fasted state may exceed those expected as a result of experimental treatment.

Testosterone and food restriction modulate hepatic lycopene isomer concentrations in male F344 rats.

We previously demonstrated that the castration of male rats profoundly increases hepatic lycopene compared with intact controls. Here we further characterized the role of testosterone in modulating hepatic lycopene accumulation and isomer patterns in male rats. Furthermore, because castration significantly decreases ad libitum food consumption, we investigated the influence of food restriction on lycopene metabolism. Forty male F344 rats 8 wk of age were randomly assigned to one of four treatments (n = 10/group): 1) intact, free access to food, 2) castration, free access to food, 3) castration plus testosterone implants, free access to food and 4) intact, 20% food restricted. All rats were fed an AIN-based diet with 0.25 g lycopene (as 10% water-soluble beadlets)/kg diet for 3 wk. Serum testosterone was 5.31 +/- 1.46 nmol/L in intact controls allowed free access to food, reduced in castrated animals (0.52 +/- 0.10, P < 0.0001 versus controls) and intact, food-restricted rats (1.53 +/- 0.49 nmol/L, P < 0.0001 versus controls) and greater (17.23 +/- 3.09 nmol/L) in castrated rats administered testosterone (P < 0.0001 versus controls). Castrated rats accumulated approximately twice as much liver lycopene (74.5 +/- 8.5 nmol/g; P < 0.01 versus controls) as intact rats allowed free access to food (39.5 +/- 5.0) despite 13% lower dietary lycopene intake (P < 0.001; 3.38 +/- 0.07 versus 3.95 +/- 0.06 mg lycopene/d). Testosterone replacement in castrated rats returned liver lycopene concentrations (32.5 +/- 5.5 nmol lycopene/g with 3.76 +/- 0.05 mg dietary lycopene/d) to those observed in intact rats. Food restriction resulted in a 20% decrease in lycopene intake but significantly increased liver lycopene by 68% (66.3 +/- 7.9 nmol lycopene/g with 3.38 +/- 0.00 mg lycopene/d) compared with controls and castrated rats administered testosterone. These results suggest that androgen depletion and 20% food restriction increase hepatic lycopene accumulation. We hypothesize an endocrine and dietary interaction, where higher androgen concentrations and greater energy intake may stimulate lycopene metabolism and degradation.

Dietary fat during pregnancy and lactation increases milk fat and insulin-like growth factor I concentrations and improves neonatal growth rates in swine.

Primiparous (n = 24) and multiparous (n = 24) sows were used to examine the effects of supplemental dietary fat and induction of parturition (d 112) on colostrum and milk composition and suckling piglet growth. Sows were assigned to one of eight treatments on d 90 of gestation that included variables such as parity (1 vs. >/=3), dietary fat (0 vs. 10%), and farrowing (natural vs. induction via lutalyse on d 112). Piglets suckling fat-supplemented dams grew up to 25% faster than control pigs nursing unsupplemented sows (250 vs. 200 g/d; P < 0.01). Improved growth was correlated with elevated milk fat and insulin-like growth factor (IGF) concentrations associated with fat supplementation. Dietary fat elevated milk fat concentration at 48 and 72 h postfarrowing by 21.6 and 22.6%, respectively (P < 0.05). Compared with nonfat-fed controls, multiparous sows fed 10% fat showed a more consistent rise in milk fat concentration, with 26% and 41% elevations for induced or naturally farrowing sows, respectively, vs. a 19% reduction or a 1% elevation in induced or naturally farrowing gilts (P < 0.01). The concentration of milk IGF-I tended to be lower in gilts than in multiparous sows (P < 0.2, 95.7 vs. 117.4 microg/L), and levels were particularly low in milk from induced gilts receiving no additional dietary fat (44.7 microg/L). However, fat supplementation elevated IGF-I to levels (110.6 microg/L) exceeding those measured in unsupplemented, naturally farrowing control sows and gilts (95.8 microg/L). In conclusion, supplemental dietary fat elevates milk fat in multiparous sows more than primiparous gilts regardless of farrowing treatment (induced vs. natural farrowing) and improves piglet growth throughout lactation irrespective of parity or farrowing treatment. The potential of supplemental dietary fat to reverse the reductions in milk IGF-I observed in first-parity females and in dams induced to farrow merits further investigation.

Enteral insulin-like growth factor-I augments intestinal disaccharidase activity in piglets receiving total parenteral nutrition.

BACKGROUND: Partial enteral nutrition is administered to infants on parenteral nutrition to stimulate intestinal function. Herein, the hypothesis that supplementation of partial enteral nutrition with insulin-like growth factor-I would augment intestinal development was investigated. METHODS: One-day-old piglets (n = 29) were randomly assigned to five dietary treatment groups: 100% of energy as enteral formula, 100% of energy as total parenteral nutrition, or 80% parenteral nutrition/20% enteral formula supplemented with either 0, 0.2, or 1 mg/kg insulin-like growth factor-I for 7 days. Weight gain, intestinal weight, morphology, protein, and DNA content and disaccharidase activity and mRNA expression were assessed. RESULTS: Parenterally fed piglets had similar whole body weight gain and serum hormone concentrations but reduced intestinal mucosal weight, villus height, and sucrase and lactase activity compared with 100% enterally fed pigs. Partial enteral nutrition alone increased mucosal weight and protein content, villus height, and disaccharidase activity compared with 100% parenterally fed piglets. No effect of the lower dose of insulin-like growth factor-I (0.2 mg/kg per day) was observed, but supplementing partial enteral nutrition with 1 mg insulin-like growth factor-I/kg further increased villus width and cross-sectional area and disaccharidase activity compared with partial enteral nutrition alone. Lactase mRNA expression was not affected by insulin-like growth factor-I, suggesting that the primary site of regulation of lactase by insulin-like growth factor-I occurs after transcription. CONCLUSIONS: Enteral insulin-like growth factor-I augmented intestinal morphology and disaccharidase activity in parenterally fed piglets over that observed with partial enteral nutrition alone. Thus enteral insulin-like growth factor-I may represent an efficacious clinical adjunct to promote intestinal development of parenterally fed neonates.

Nutritional aspects of manganese from experimental studies.

In experimental animals, dietary manganese deficiency can result in numerous biochemical and structural abnormalities. Deficient animals can be characterized by impaired insulin production, alterations in lipoprotein metabolism, an impaired oxidant defense system, and perturbations in growth factor metabolism. If the deficiency occurs during early development, there can be pronounced skeletal abnormalities and an irreversible ataxia. Several lines of evidence suggest that manganese deficiency may be a problem in some human populations. Manganese toxicity can also pose a significant health risk. In experimental animals, acute manganese toxicity can result in numerous biochemical pathologies. However, the above occurs typically when the manganese is given via injection; most animals show considerable resistance to dietary manganese toxicosis. Similarly, confirmed cases of manganese toxicity in humans are currently restricted to cases of exposure to high levels of airborne manganese, and to cases when manganese excretory pathways are compromised.

The influence of manganese deficiency on serum IGF-1 and IGF binding proteins in the male rat.

Young male rats subjected to a dietary manganese (Mn) deficiency respond to the deficiency by reducing their growth rate. The growth hormone (GH)/insulin-like growth factor (IGF) axis is critical for linear growth; this system is exquisitely sensitive to the nutritional state of the animal. In this study, we examined circulating GH, IGF-1, and insulin levels in Mn-deficient (-Mn; fed a 0.5 microg Mn/g diet) and sufficient (+Mn; fed a 45 microg Mn/g diet) male Sprague-Dawley rats. Additionally, we examined the distribution of circulating IGF binding proteins (IGFBPs) in animals of both dietary groups as these proteins modulate IGF-1 action in vivo and in vitro, and have been demonstrated to be altered in a number of nutritional and physiological states. Body weight was significantly reduced in -Mn relative to +Mn rats. Consistent with other studies, daily food intake was not altered. However, cumulative food intake (over 3 months) was marginally lower in -Mn versus +Mn animals. -Mn animals displayed lower circulating concentrations of IGF-1 (66% of control levels) and insulin (60% of control levels) despite having significant elevations in circulating GH levels relative to +Mn animals (140% of control levels). The IGFBP profile of -Mn animals reflected their elevated GH status, as we observed increased binding of tracer (125I-IGF-1) to the circulating IGFBP-3 complex (120% of control binding) using native chromatography techniques. Interestingly, the lower circulating insulin concentrations of -Mn animals did not result in dramatic elevations in lower-molecular-weight binding proteins. In summary, we demonstrate that in young male rats, Mn deficiency is associated with alterations in IGF metabolism. These alterations may contribute to the growth and bone abnormalities observed in -Mn animals.

Moderate food restriction reduces serum IGF-I and alters circulating IGF-binding protein profiles in lactating rats.

The role of somatogenic and lactogenic hormones in the adaptative mechanisms which occur in response to nutrient restriction during lactation is unknown. To characterize the effect of food restriction during lactation on serum IGF-I, GH and prolactin concentrations and serum IGF-binding protein (IGFBP) profiles, lactating dams had free access to food (control) or were restricted to 60% of control intake during pregnancy and lactation (RPL) or only during lactation (RL). Serum, milk and mammary gland samples were collected throughout lactation. RL dams lost body weight, control dams gained weight, while RPL dams maintained body weight during lactation. By day 20, body and mammary gland weights of RL and RPL dams did not differ and were lower than control (P < 0.05). Serum IGF-I concentrations in restricted groups were lower than control (P < 0.05), however, hepatic expression of IGF-I mRNA did not differ between groups in early (day 1) or mid-lactation (day 8) and was increased on day 20 in RL dams compared with RPL or control. These data suggest that serum IGF-I and hepatic IGF-I mRNA expression are not co-ordinately regulated in the food-restricted lactating rat. In early lactation, serum IGFBP-3 was lower in RPL dams than control (P < 0.05), whereas IGFBP-1 and -2 were increased in RL and RPL dams in late lactation compared with control. The decrease in IGFBP-3 and increase in lower molecular weight IGFBP may have contributed to the reduction in serum IGF-I by increasing IGF-I clearance from the circulation. Serum GH and prolactin were measured in samples obtained between 0900 and 1200 h. Serum GH did not differ with the exception of an increase on day 1 in control relative to RPL dams and on day 20 in RL dams relative to RPL and control. Serum prolactin was higher in the RL dams than controls on day 4. In summary, food restriction during pregnancy and lactation or solely during lactation results in similar reductions in serum IGF-I and alterations in serum IGFBP despite differences in body weight responses to food restriction during lactation.

Moderate food restriction abolishes the pregnancy-associated rise in serum growth hormone and decreases serum insulin-like growth factor-I (IGF-I) concentrations without altering IGF-I mRNA expression in rats.

Pregnancy-associated growth of maternal and fetal tissues is likely mediated by insulin-like growth factors (IGF). To study the effect of food restriction during pregnancy on the IGF system, pregnant rats either had free access to food (control) or were fed 60% of control food intake. Serum and liver samples were obtained throughout gestation. Serum IGF-I and growth hormone (GH) concentrations were measured by RIA, and IGF binding proteins (IGFBP) were characterized by Western ligand blotting and gel filtration chromatography. Weight gain of control dams was nearly twice that of restricted dams. Litter size was not significantly different; however, fetuses and placentas of restricted dams were 20% smaller than those of controls. Serum IGF-I concentrations on d 20 were 35 and 23% of d 5 concentrations in control and restricted pregnant rats, respectively. However, hepatic IGF-I mRNA did not differ between the treatment groups. A pregnancy-associated rise in serum GH was observed in control but not food-restricted dams. Insulin-like growth factor binding protein with apparent molecular retention of 38-42 kDa (IGFBP-3), 29-31 kDa and 24 kDa were apparent in serum of pregnant dams in early gestation; however, IGFBP-3 was no longer detected by Western ligand blot by d 15 of gestation. The decline in IGFBP-3 was accompanied by an increase in IGFBP-1 and -2, particularly in the serum of food-restricted dams. These data suggest that in food-restricted pregnant rats, serum IGF-I and IGF-I mRNA are insensitive to serum GH concentrations and are not regulated at the level of transcription.