epidermal-growth-factor and Weight-Gain

The abnormalities in intestinal morphology and digestive function during weaning are associated with the loss of milk-borne growth factors. Epidermal growth factor (EGF) has been shown to stimulate the growth of animals. This study was to determine the effect of dietary EGF on nutrient digestibility, intestinal development and the expression of genes encoding nutrient transporters in weaned piglets. Forty-two piglets were weaned at 21 days and assigned to one of three treatment groups: (1) basal diet (control), (2) basal diet + 200 µg/kg EGF or (3) basal diet + 400 µg/kg EGF. Each treatment consisted of 14 replicates, and seven piglets from each treatment were sampled on day 7 and 14. The EGF supplementation significantly elevated (p < 0.05) the coefficients of total tract apparent digestibility of crude protein, calcium and phosphorus, but tended to decrease sucrase activity (p < 0.10) than the control group. At day 7 post-weaning, animals receiving EGF diets showed a tendency (p < 0.10) towards greater ileal villus height (VH), jejunal crypt depth (CD) and duodenal VH:CD when compared with the control group. Moreover, the mRNA levels of glucose transporter 2 (Slc2a2), neutral amino acid transporter (Slc6a19) and calbindin D9k (S100G) tended to be higher (p < 0.10) for EGF groups than the control group. By day 14, EGF supplementation markedly enhanced (p < 0.05) the VH, CD and VH:CD in the jejunum compared to the control group. This addition also up-regulated (p < 0.05) the mRNA level and the protein abundance of peptide transporter 1 than the control group. These findings demonstrated that dietary EGF beneficially enhanced nutrient digestibility, improved intestinal development and increased the mRNA expression of nutrient transporters in weaned piglets.

Topics: Animals; Carrier Proteins; Digestion; Epidermal Growth Factor; Gene Expression Regulation; Intestines; Nutrients; Random Allocation; Swine; Weaning; Weight Gain

The effect of supplementing Lactococcus lactis (L. lactis) that was engineered to express epidermal growth factor (EGF-LL) to early-weaned pigs fed diets with typical levels of blood plasma (5%) or diets without blood plasma [blood plasma was substituted with soybean (Glycine max) meal and fish meal, based on amino acid supply] was examined. A total of 108 weaned piglets (19-26 d of age; mean initial BW 6.58 kg; 9 pigs per pen) were fed ad libitum according to a 2-phase feeding program without growth promoters. Three pens were assigned to each of 4 treatments: i) blood plasma-containing diet with blank bacterial growth medium (BP-Con), ii) blood plasma-containing diet with fermented EGF-LL (BP-EGF), iii) blood plasma-free diet with blank bacterial growth medium (BPF-Con), and iv) blood plasma-free diet with fermented EGF-LL (BPF-EGF). The amount of epidermal growth factor (EGF) was determined in the fermentation product and pigs were allotted 60 μg EGF/kg BW/d for 3 wk postweaning. There were no differences in overall growth performance between BP-Con and BP-EGF pigs and no differences in overall growth performance between LoCon and BPF-EGF pigs. Pigs fed BPF-EGF showed increased daily BW gain (410 vs. 260 g/d; P < 0.01) and gain:feed (0.67 vs. 0.58; P < 0.05) compared to BPF-Con pigs in wk 3 postweaning; this was comparable to values for the BP-Con group (400 g/d and 0.64). These results indicate that supplementation with EGF-LL can be effective in enhancing the performance of early-weaned piglets fed a low complexity diet and reduces the need for feeding high-quality animal proteins and antibiotics.

Topics: Animal Feed; Animals; Diet; Dietary Supplements; Epidermal Growth Factor; Female; Lactococcus lactis; Male; Plasma; Probiotics; Swine; Weight Gain

This study examined the effects of enterally administered epidermal growth factor (EGF) on nutrient absorption and tolerance of enteral feeds in pediatric patients with short bowel syndrome (SBS).. Patients identified with severe SBS (<25% bowel length predicted for age) were prospectively enrolled in treatment using human recombinant EGF (1-53); 100 microg/kg per day given mixed with enteral feeds and patients were treated for 6 weeks. End points followed were patient weight, tolerance of enteral feeds, nutrient absorption, and intestinal permeability as determined using carbohydrate probes and hematologic values for liver function parameters.. Five patients were treated with EGF; all showed a significant improvement in carbohydrate absorption (3-0 methylglucose): absorption 24.7% +/- 9.7% pretreatment vs 34.1% +/- 13.8% posttreatment and improved tolerance of enteral feeds (enteral energy as % of total energy, 25% +/- 28% pretreatment vs 36% +/- 24% posttreatment; mean +/- SD; P < .05 by Wilcoxon's signed rank test). Epidermal growth factor treatment was not associated with significant changes in intestinal permeability, the rate of weight gain, or liver function tests. During the treatment phase, no patients developed episodes of sepsis; however, within 2 weeks of discontinuation of EGF treatment, 3 patients developed septic episodes. No adverse effects of EGF administration were noted.. These results suggest that enteral treatment with EGF in pediatric SBS improves nutrient absorption, increases tolerance with enteral feeds, and may improve the infection rate. Further studies exploring treatment strategies including the timing and duration of EGF administration are indicated.

Topics: 3-O-Methylglucose; Child, Preschool; Dietary Carbohydrates; Enteral Nutrition; Enterocolitis, Necrotizing; Epidermal Growth Factor; Gastroschisis; Humans; Infant; Infant Food; Intestinal Absorption; Intestinal Volvulus; Lactulose; Liver Function Tests; Male; Mannitol; Pilot Projects; Postoperative Complications; Recombinant Proteins; Sepsis; Short Bowel Syndrome; Weight Gain

We have previously generated epidermal factor expressing Lactococcus lactis (EGF-LL) using a bioengineering approach, and shown that EGF-LL fermentation supernatant enhanced newly weaned pigs growth. The objective of the current study was to further understand the mechanisms behind this improved performance. Sixty-four piglets were weaned at 3 weeks of age and then fed ad libitum according to a 2-phase feeding program. Four pens with 8 pigs per pen were assigned to each of two treatments for 3 weeks: (1) EGF containing supernatant from EGF-LL culture (SuperEGF) or (2) blank M17GE media (Control). Consistent with previous findings, SuperEGF pigs had an increased average daily gain during week 3 post-weaning (433.4 ± 10.86 vs 388.7 ± 7.76 g; P<0.05) and overall gain:feed ratio (0.757 ± 0.03 vs 0.677 ± 0.01 kg/kg, P < 0.05). Moreover, jejunal structure development was enhanced, and inflammation index was minimized in SuperEGF pigs as indicated by increased villi height (P<0.05), decreased lamina propria width (P<0.05), and higher expression of anti-inflammatory cytokine, IL-13 (P<0.05). Further, goblet cell numbers and Muc2 levels were increased in SuperEGF pigs. Interestingly, the weaning-induced decrease of glucose cotransporter sodium-glucose linked transporter 1 (SGLT1) and glucagon-like peptide-2 (GLP2) levels was reversed by SuperEGF supplementation. Our findings add to our understanding of the mechanisms behind enhancing piglet performance by EGF containing fermentation product.

Topics: Animal Feed; Animals; Diet; Epidermal Growth Factor; Fermentation; Glucose Transporter Type 2; Jejunum; Lactococcus lactis; Receptor, IGF Type 1; Sodium-Glucose Transporter 1; Swine; Weaning; Weight Gain

We have previously generated epidermal growth factor expressing Lactococcus lactis (EGF-LL) using bioengineering approach, and shown that feeding newly-weaned piglets EGF-LL improves digestive function. To address concerns over the use of genetically modified organisms (GMO), the objective of the current study was to investigate the effect of feeding the EGF-LL fermentation product, after removal of the genetically modified EGF-LL, on growth performance and intestine development of newly-weaned piglets. One hundred and twenty newly-weaned piglets were fed ad libitum according to a 2-phase feeding program. Four pens were assigned to each of three treatments: (1) complete EGF-LL fermentation product (Ferm), (2) supernatant of EGF-LL fermentation product, after removal of EGF-LL (Supern), or (3) blank M17GE media (Control). EGF-LL or its fermented supernatant was administrated to piglets in the first 3 weeks post-weaning; their growth performance was monitored throughout treatment, and for the following week. Daily body weight gain (254.8g vs. 200.5g) and Gain:Feed (0.541kg/kg vs. 0.454kg/kg) of pigs on the Supern group were significantly improved compared to that of Control, although no difference was observed between the Ferm and Control pigs. Intestinal sucrase activity was increased in Supern- compared to Control group (166.3±62.1 vs. 81.4±56.5nmol glucose released/mg protein; P<0.05). The lack of growth response with Ferm pigs may be attributed to an overload of bacteria (daily dose included 4.56×10(10)CFU/kg BW/day EGF-LL). These results suggest that GMO-free EGF-LL fermentation product is effective in increasing growth performance of early-weaned piglets.

Topics: Animal Feed; Animals; Diet; Dietary Supplements; Epidermal Growth Factor; Female; Fermentation; Lactococcus lactis; Male; Probiotics; Swine; Weight Gain

To investigate the effect of epidermal growth factor (EGF) on mucosal healing in rats with duodenal ulcer.. Male Sprague-Dawley rats were randomly divided into sham operation without EGF, sham operation with EGF, duodenal ulcer without EGF, or duodenal ulcer with EGF groups. Additionally, normal rats without operation served as the control group. Duodenal ulcer was induced in rats by 300 mL/L acetic acid. Rats with EGF were orally administered at a dose of 60 microg/kg/day in drinking water on the next day of operation (day 1). Healing of duodenal ulcer was detected by haematoxylin and eosin staining. Cell growth of damaged mucosa was determined by the contents of nucleic acids and proteins. The level of EGF in duodenal mucosa was measured by ELISA.. The pathological results showed that duodenal ulcer rats with EGF improved mucosal healing compared with those without EGF after day 5. Duodenal ulcer rats with EGF significantly increased duodenal DNA content compared with those without EGF on day 15 (6.44+/-0.54 mg/g vs 1.45+/-0.52 mg/g mucosa, P<0.05). Duodenal RNA and protein contents did not differ between duodenal ulcer rats with and without EGF during the experimental period. Sham operation and duodenal ulcer rats with EGF significantly increased duodenal mucosal EGF content compared with those without EGF on day 5 (76.0+/-13.7 ng/g vs 35.7+/-12.9 ng/g mucosa in sham operation rats, and 68.3+/-10.9 ng/g vs 28.3+/-9.2 ng/g mucosa in duodenal ulcer rats, P<0.05).. Oral EGF can promote mucosal healing of the rats with duodenal ulcer by stimulating mucosal proliferation accompanied by an increase in mucosal EGF content.

Topics: Acetic Acid; Administration, Oral; Animals; DNA; Duodenal Ulcer; Eating; Epidermal Growth Factor; Intestinal Mucosa; Male; Proteins; Rats; Rats, Sprague-Dawley; RNA; Weight Gain; Wound Healing

Necrotizing enterocolitis (NEC) is the most common gastrointestinal disease of prematurely born infants. Maternal milk plays an important protective role against NEC development and is the major source of epidermal growth factor (EGF) for neonates. The aim of this study was to examine the effect of orally administered EGF on the incidence of NEC in a neonatal rat model. Newborn rats were artificially fed either with growth factor-free rat milk substitute (RMS) or RMS supplemented with 500 ng/ml of EGF (RMS+EGF). Experimental NEC was induced by exposure to asphyxia and cold stress. Development of NEC was evaluated by gross and histological scoring of damage in the ileum. Ileal EGF receptor (EGF-R), EGF, and transforming growth factor-alpha mRNA expression was assessed by RT competitive-PCR, and the EGF-R was localized by immunohistochemistry. EGF supplementation of formula reduced the incidence and severity of NEC in rats (13/16 RMS vs. 4/13 RMS+EGF). Ileal EGF-R mRNA expression was markedly increased in the RMS group compared with RMS+EGF. Enhanced EGF-R expression in the RMS group was localized predominantly in the epithelial cells of injured ileum. These data suggest a new potential therapeutic approach for the prevention and treatment of NEC.

Topics: Animals; Animals, Newborn; Disease Models, Animal; Enterocolitis, Necrotizing; Epidermal Growth Factor; ErbB Receptors; Gene Expression; Ileum; Incidence; Milk; Rats; Rats, Sprague-Dawley; RNA, Messenger; Transforming Growth Factor alpha; Weight Gain

This study investigates the effect of epidermal growth factor (EGF) on nutrient absorption in a rat model of short bowel syndrome (SBS).. Male juvenile rats underwent either transection (Sham) or ileocecal resection leaving a 20-cm jejunal remnant. Animals underwent follow-up for 10 days, and resected animals were treated with placebo or recombinant human EGF (1-53). Animals were pair fed; in vivo nutrient absorption, intestinal permeability, morphology, and total intestinal DNA and protein content were measured.. Resected EGF-treated animals lost significantly less weight than those in the placebo group (-4.2 +/- 3 v -13.7 +/- 6.9%), absorbed significantly more 3-0 methylglucose (76.8 +/- 6.6 v 64.9 +/- 10.1%), and had reduced permeability (lactulose/mannitol ratio, 0.35 +/- 0.19 v 0.60 +/- 0.20; P <.05 for all comparisons).. These findings show that treatment of short bowel syndrome animals with EGF reduced weight loss and improved carbohydrate absorption and intestinal permeability. These findings suggest that enteral EGF may be a useful therapy for short bowel syndrome; further studies are indicated.

Topics: Absorption; Animals; Dietary Carbohydrates; Dietary Fats; Dietary Proteins; Disease Models, Animal; Epidermal Growth Factor; Male; Nutrition Assessment; Rats; Rats, Sprague-Dawley; Short Bowel Syndrome; Treatment Outcome; Weight Gain

To assess effects of supraphysiologic doses of human recombinant epidermal growth factor(1-48) (rhEGF(1-48)) on neonatal rats, 10 litters of Wistar rats/treatment group were given 0 (formulated vehicle), 10, 100, or 1000 microg/kg daily by subcutaneous injection on postnatal days (PND) 1 through 6. Clinical signs, body weight, acquisition of developmental landmarks and reflexes, and behavior were monitored during treatment and for 5 weeks thereafter (to PND 42). A subset of animals was euthanized weekly from PND 7-28 and necropsied. Selected tissues were examined microscopically. Body weight gain at 1000 microg/kg during treatment was significantly less than control. Precocious incisor eruption, eye opening, vaginal opening, and preputial separation occurred at 100 and/or 1000 microg/kg. Acquisition of reflexes (negative geotaxis, wire maneuver, acoustic startle reflex, and visual placing) was delayed at 1000 microg/kg. Acquisition of adult locomotion was also delayed at 1000 microg/kg. These effects were transient, as locomotor activity at PND 28 and 42 did not differ from control. Effects on acoustic-startle responding persisted in females to final assessment on PND 42. Habituation to repeated acoustic stimuli was impaired, as well as response inhibition following a prepulse acoustic stimulus. rhEGF(1-48) induced structural changes in the skin, retina, kidney, oral and nasal mucosa, lung, and liver. Many of these changes were consistent with the expected mitogenic activity of rhEGF(1-48) and were transient in nature, as severity and incidence diminished with time. An exception was changes observed in the retina at 1000 microg/kg (rosettes/folds and focal defects in the outer nuclear/photoreceptor layers) that were still present 3 weeks after termination of treatment. Acceleration of developmental landmarks; suppression of reflexes, behavior, and somatic growth; and mitogenic responses in epidermal tissues have been reported in rodents treated with epidermal growth factor (EGF) derived from various mammalian species. These results demonstrate that a 48-amino acid fragment of human EGF produced by recombinant technology also induces such effects.

Topics: Acoustic Stimulation; Animals; Animals, Newborn; Behavior, Animal; Dose-Response Relationship, Drug; Epidermal Growth Factor; Female; Genitalia; Injections, Subcutaneous; Mitogens; Motor Activity; Neural Inhibition; Organ Size; Peptide Fragments; Pregnancy; Rats; Rats, Wistar; Recombinant Proteins; Sexual Maturation; Skin; Toxicity Tests; Weight Gain

The increased intestinal absorption induced by epidermal growth factor (EGF) is associated with diffuse lengthening of brush border microvilli. The aim of this study was to examine the in vivo effects of oral administration of EGF during infection with enteropathogenic Escherichia coli. New Zealand White rabbits (4 weeks old) received orogastric EGF daily starting 3 days prior to infection with enteropathogenic E. coli RDEC-1 and were compared with sham-treated infected animals and uninfected controls. Weight gain, food intake, fecal E. coli, and stool consistency were assessed daily. On day 10, segments of jejunum, ileum, proximal, and distal colon were assessed for gram-negative bacterial colonization, disaccharidase activities, and epithelial ultrastructure. Effects of EGF on E. coli RDEC-1 proliferation were studied in vitro. E. coli RDEC-1 caused diarrhea and reduced weight gain. Seven days postinfection, the small and large intestines were colonized with numerous bacteria, brush border microvilli were disrupted, and maltase and sucrase activities were significantly reduced in the jejunum. Daily treatment with EGF prevented the occurrence of diarrhea and reduction of weight gain. These effects were associated with significant inhibition of E. coli colonization in the small and large intestine, improved jejunal maltase and sucrase activities and reduced microvillous injury. EGF did not affect the proliferation of E. coli in vitro. The findings suggest that EGF protects the gastrointestinal tract against colonization by enteropathogenic E. coli.

Topics: Administration, Oral; Animals; Diarrhea; Epidermal Growth Factor; Escherichia coli; Escherichia coli Infections; Intestinal Diseases; Intestine, Large; Intestine, Small; Microvilli; Rabbits; Weight Gain

Pregnant rats were subcutaneously administered with mouse epidermal growth factor (EGF) at the concentration of 0, 100, or 200 micrograms/kg body weight/day from day 18 to 21 of gestation. The amino acid analysis by high-performance liquid chromatography demonstrated that the umbilical venous/maternal and fetal/maternal ratio of serum proline concentration increased in EGF dose-dependent manner accompanied by the increase in the ratios of total fetal weight and placental weight to maternal body weight gain. These results suggested that EGF regulates fetal growth by, as one of its possible mechanism, promoting placental proline supply from mother to fetus.

Topics: Amino Acids; Animals; Chromatography, High Pressure Liquid; Epidermal Growth Factor; Female; Fetal Blood; Fetus; Injections, Subcutaneous; Maternal-Fetal Exchange; Mice; Pregnancy; Proline; Rats; Rats, Wistar; Umbilical Veins; Weight Gain

Aged mice exhibit an increase in their body weight (BW), which is associated with fat deposit increase. Epidermal growth factor (EGF) concentration in the submandibular gland also increases with aging. We examined the effects of elevated EGF on the adiposity of aged female mice. Studies were started in two groups of animals consisting of sham-operated (n = 10) and sialoadenectomized (n = 10, Sx; surgical removal of the submandibular glands) mice at 8 weeks of age. Body weight gain and food intake were measured throughout 78 weeks of age in these two groups. Body weight was significantly less in the Sx group throughout 78 weeks, while food intake was not changed by Sx after 12 weeks of age. To examine further if EGF plays a role in the induction of adiposity in aged female mice, sham-operated animals were given 100 microliters anti-EGF rabbit antiserum (anti-EGF group, n = 5) or normal rabbit serum (control group, n = 5) every 3 days, and Sx animals were given 5 micrograms/day EGF (Sx+EGF group, n = 5) or saline (Sx group, n = 5) from 78 weeks of age for 3 weeks. At 81 weeks of age, all animals of these four groups were killed, and carcass fat deposition and fat cell sizes were measured. Although the relative weights (weight ratio to BW) of the liver and kidney were not changed by Sx and anti-EGF treatment, the relative weights of mesenteric and subcutaneous fat tissues and adipocyte weights were significantly decreased in Sx and anti-EGF groups compared with the control group. Moreover, both acyl-CoA synthetase (ACS) and lipoprotein lipase (LPL) mRNA levels were significantly decreased by Sx or anti-EGF administration in mesenteric and subcutaneous fat tissues. On the other hand, EGF administration to Sx animals had no effect on BW, fat tissues and adipocyte weights, and ACS and LPL mRNA levels. The results, however, were consistent with the fact that adipose tissue EGF receptors were down regulated in Sx mice. These findings suggest that EGF may play a role in the induction of adiposity in aged female mice.

Topics: Adipose Tissue; Aging; Animals; Coenzyme A Ligases; Down-Regulation; Energy Intake; Epidermal Growth Factor; ErbB Receptors; Female; Immune Sera; Lipoprotein Lipase; Mice; Mice, Inbred C3H; Saliva; Submandibular Gland; Time Factors; Weight Gain

A study was performed to attempt to modify the healing response to severe oesophageal corrosive burns to prevent complications. The study was performed on four groups each of 15 Wistar rats: a control group, an untreated group and groups given epidermal growth factor (EGF) alone or EGF for 5 days and interferon (IFN) gamma from the sixth to 20th day. In the last three groups an oesophageal lesion was induced with 2.5 mol l-1 sodium hydroxide solution. The efficacy of treatment was assessed on days 2, 5 and 20 by measurement of weight gain, oesophageal internal lumen, stenosis index (wall thickness: lumen diameter) and collagen production. On day 5, collagen synthesis was significantly (P < 0.05) higher in rats given EGF than in the untreated group. On day 20, no significant difference was seen in weight gain between the control rats and either treated group and stenoses were present in all untreated rats and in none of the treated group. The stenosis index on day 20 was lower in the groups given EGF and EGF-IFN-gamma than in untreated rats (P < 0.05) and collagen production was significantly (P < 0.05) lower in the group given EGF and IFN-gamma than in the other animals. The sequential use of EGF and IFN-gamma significantly reduced the frequency of residual stenosis.

Topics: Animals; Burns, Chemical; Collagen; Drug Therapy, Combination; Epidermal Growth Factor; Esophageal Stenosis; Esophagus; Hydroxyproline; Interferon-gamma; Male; Random Allocation; Rats; Rats, Wistar; Sodium Hydroxide; Weight Gain; Wound Healing

This study evaluates the effect of dietary wheat bran on the levels of immunoreactive epidermal growth factor (EGF) in the gastrointestinal mucosa of Fischer 344 rats. Male rats were fed either a fiber-free diet or a diet containing 10% wheat bran (nine animals per group) for a period of 5 wk. The gastrointestinal tract of each animal was divided into four segments: proximal, middle and distal small intestine, and colon. Mucosa was removed by scraping, EGF was extracted by homogenization and the extracts were analyzed for immunoreactive rat EGF using a homologous RIA. Levels of immunoreactive EGF in all regions of the small intestine of Fischer rats were comparable to our previous measurements in Sprague-Dawley rats, and these levels were unaffected by diet. In contrast, the EGF levels in the colon of the Fischer rats were approximately fivefold greater than those of the Sprague-Dawley rats. These higher levels of immunoreactive EGF in the colon decreased 63% with the addition of 10% wheat bran to the diet (P less than 0.02). These results represent the first demonstration of dietary fiber modulating the content of EGF in the gastrointestinal tract.

Topics: Animals; Diet, Reducing; Eating; Epidermal Growth Factor; Intestinal Mucosa; Male; Proteins; Radioimmunoassay; Rats; Rats, Inbred F344; Rats, Inbred Strains; Triticum; Weight Gain