leptin and Swine-Diseases

To understand why sick animals do not eat, investigators have studied how the immune system interacts with the central nervous system (CNS), where motivation to eat is ultimately controlled. The focus has been on the cytokines secreted by activated mononuclear myeloid cells, which include interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha). Either central or peripheral injection of recombinant IL-1 beta, IL-6, and TNF-alpha reduce food-motivated behavior and food intake in rodents. Moreover, these cytokines and their receptors are present in the endocrine system and brain, and antagonism of this system (i.e., the cytokine network) has been shown to block or abrogate anorexia induced by inflammatory stimuli. Recent studies indicate that the same cytokines act on adipocytes and induce secretion of leptin, a protein whose activity has been neuroanatomically mapped to brain areas involved in regulating food intake and energy expenditure. Therefore, many findings converge to suggest that the reduction of food intake in sick animals is mediated by inflammatory cytokines, which convey a message from the immune system to the endocrine system and CNS. The nature of this interaction is the focus of this short review.

Topics: Adaptation, Physiological; Adipose Tissue; Animals; Anorexia; Central Nervous System; Chickens; Cytokines; Eating; Immune System; Inflammation; Leptin; Mice; Neuroimmunomodulation; Poultry Diseases; Proteins; Rats; Swine; Swine Diseases

Ovarian follicular cysts are one of leading causes of infertility and financial loss in pig breeding program. This study was carried out to investigate the association between polymorphisms of estrogen receptor (ESR), follicle-stimulating hormone (FSH) β, and leptin genes and follicular cysts in sows. A total of 47 and 120 sows with follicular cysts and normal follicles, respectively, were selected to evaluate whether these candidate loci affect the formation of follicular cysts in sows. The polymorphisms of ESR, FSHβ, FSHβ/HaeIII and leptin genes were tested by PCR and PCR-RFLP methods. Cyst-normal case data analysis showed that ESR/PvuII polymorphisms are highly associated with follicular cysts and that sows ESR/PvuII genotype have lower rate of suffering from cysts (P = 0.021). Unfortunately, FSHβ, FSHβ/HaeIII, and leptin C3469T polymorphisms were found no significant difference in follicular cysts sows and normal sows. These results suggest that FSHβ, FSHβ/HaeIII, and leptin C3469T genotypes are not able to effect the presence of follicular cysts (P > 0.05). In addition, the haplotype EBCM and EBTM within four loci of genes had significant dominance effect on follicular cysts (P < 0.05). The detection of ESR/PvuII polymorphisms and haplotype EBCM and EBTM can positively improve the development of biological biomarkers, which is thereby beneficial in breeding and ovary-protective therapy of reproductive disease in pigs.

Topics: Animals; Case-Control Studies; Deoxyribonucleases, Type II Site-Specific; Female; Follicle Stimulating Hormone, beta Subunit; Genetic Predisposition to Disease; Leptin; Ovarian Cysts; Polymorphism, Genetic; Receptors, Estrogen; Swine; Swine Diseases

Previous studies indicate that reproductive prolificacy of obese swine breeds is markedly influenced by embryo losses in early pregnancy. In such period, adequate secretion of progesterone (P4) by the ovary is essential for pregnancy success. This study analyses the luteal functionality during the oestrous cycle and early pregnancy of Iberian sows and Large White x Landrace females, in terms of P4 secretion after in vitro culture of luteal tissue stimulated or not with luteinizing hormone (LH). The secretion of progesterone (expressed in ng/mg of luteal tissue or ng/mgLT) of the corpora lutea of obese Iberian swine was always hampered when compared to lean genotypes, either during early oestrous cycle (110.7 ± 37.8 vs 259.7 ± 10.2 ng/mgLT; p < 0.0001), late oestrous cycle (49.0 ± 3.5 vs 75.92 ± 7.14 ng/mgLT; p < 0.0001) or early pregnancy (38.4 ± 2.1 vs 70.7 ± 5.3 ng/mgLT; p < 0.0001). The differences in basal P4 secretion remained after stimulation with LH. Finally, P4 secretion during early pregnancy of Iberian sows decreased with age and, hence, with obesity features (46.6 ± 4.2 vs 65.5 ± 4.8 ng/mgLT; p < 0.001). In conclusion, the results of the present study provide convincing evidence of a reduced luteal function during oestrous cycle and early pregnancy of sows with obesity/leptin resistance like Iberian sows, which may contribute to the low reproductive efficiency reported in this breed.

Topics: Animals; Estrous Cycle; Female; Leptin; Obesity; Ovary; Pregnancy; Progesterone; Swine; Swine Diseases

Iberian pig is the most abundant Mediterranean swine. The lack of knowledge of the reproductive physiology of Mediterranean genotypes, with predisposition to obesity, led us to evaluate the influence of body condition and metabolic status at weaning on the resumption of follicular growth and the appearance of post-weaning oestrus. Females failing to display post-weaning oestrus showed a high decrease in backfat mass during lactation; backfat depth at weaning was therefore lower than in sows becoming in oestrus. Females not bearing oestrus behaviour showed lower plasma leptin levels and higher ghrelin concentrations at weaning. Moreover, these sows evidenced dyslipidemic profile (increased triglyceridemia and cholesterolemia) and mobilization of fat reserves. Hence, changes in metabolic regulation of Iberian pigs may originate large effects on the resumption of ovulatory activity after weaning.

Topics: Adiposity; Animals; Blood Glucose; Estrus; Female; Ghrelin; Hyperlipidemias; Leptin; Lipids; Obesity; Sus scrofa; Swine Diseases; Weaning

This trial examined the effects of feeding six diets, which varied in either amount or composition, during the oestrous cycle prior to insemination on embryo survival and foetal development on day 27+/-2 of pregnancy in gilts. Ten or 11 gilts per group received either a maintenance (M) diet, 1.8 x M, 2.6 x M or nutritionally balanced diets in which the content of fibre, protein or starch was increased. Of the six diets tested, only the high fibre diet significantly increased embryo survival when compared to its 1.8 x M isoenergetic control (88.20+/-1.96% versus 81.25+/-2.67%; P<0.05). More litters from gilts fed the 1.8 x M and the starch diets had foetuses defined as intra-uterine growth retarded (IUGR; 50% and 62.5 of litters, respectively), compared to the other four groups in which 0-12.5% of litters contained IUGR foetuses (P<0.05). There was no effect of dietary treatment on foetal or placental size or on the within-litter variability in foetal and placental size. Plasma concentrations of oestradiol and progesterone on days 4-8 of the oestrous cycle and on day 27+/-2 of pregnancy were unaffected by treatment. Feed intake was positively related to mean plasma IGF-1 concentrations on days 4-8 of the cycle (P<0.01) and to mean leptin concentrations on days 4 and 5 (P<0.001). Leptin concentrations were unaffected by alterations in the composition of the diet, whereas IGF-1 concentrations were higher in gilts fed the starch diet compared to the M control (159+/-9.52 versus 127+/-7.65 ng/ml; P<0.05). These data demonstrate that alteration to the composition of the feed consumed during the cycle before insemination can affect both embryo survival and the distribution of foetal size within the litter. The underlying mechanism(s) remain to be determined, but probably involve dietary-induced changes in concentrations of reproductive hormones and/or intermediary metabolites that in turn affect ovarian follicular and oocyte development.

Topics: Adipose Tissue; Animal Nutritional Physiological Phenomena; Animals; Body Composition; Body Weight; Diet; Dietary Fiber; Dietary Proteins; Embryo, Mammalian; Estradiol; Female; Fetal Development; Fetal Growth Retardation; Fetal Weight; Insulin-Like Growth Factor I; Leptin; Organ Size; Placenta; Pregnancy; Progesterone; Starch; Swine; Swine Diseases

One of the hallmarks of the pathophysiology of enteric disease in young pigs is reduced growth performance. This reduction in growth is associated with changes in the endocrine somatotropic growth axis. Our laboratory previously demonstrated that circulating insulin-like growth factor-I (IGF-I) was reduced in pigs infected with Salmonella enterica serovar Typhimurium (S. typhimurium) while circulating growth hormone remained unchanged. The objective of the current study was to determine if infection with S. typhimurium also was associated with changes in circulating IGF binding proteins (IGFBP). In addition, pigs experiencing active enteric disease have reduced feed intake. Because this inappetence may be related to systemic appetite reduction signals, we also evaluated circulating leptin in pigs undergoing active S. typhimurium-induced enteric disease. Crossbred pigs were penned in environmentally controlled rooms with free access to feed and water. Following an acclimation period, pigs were gavaged with 10(10) cfu of S. typhimurium (SAL; n=6) or were given a similar volume of sterile growth media (CON; n=6). Rectal temperatures and feed intakes were measured daily through 168 h to track the time course of the response to S. typhimurium infection. Samples of serum were obtained by jugular venipuncture at 0, 24, 48, 96 and 168 h after infection. Sera were frozen until evaluation for IGF-I by immunoradiometric assay (IRMA). In addition, sera were subjected to western ligand blotting utilizing 125I-IGF-I and 125I-IGF-II. Images were evaluated for total IGFBP and IGFBP-3 by densitometric analyses. Rectal temperature was increased in SAL pigs 24h post-infection (P<0.001) but not at other times. Feed intake was reduced in SAL pigs during the intervals 24-72 h (P<0.001) and 96-144 h (P<0.05) after infection. Serum IGF-I, expressed as a percentage of the 0 h concentration, was reduced in SAL pigs versus CON pigs at 48 h (28.1+/-18.7% versus 102.2+/-17.1%; P<0.01) and 96 h (20.0+/-18.7% versus 128.4+/-17.0%; P<0.0001) post-infection. Both total IGFBP and IGFBP-3, as estimated by ligand blotting, also were reduced in infected pigs at 48 h postchallenge (P<0.05). IGFBPs were similar between the two treatments at other sampling times. Concentrations of IGFBP-3 also were estimated utilizing an IRMA for human IGFBP-3. Serum IGFBP-3 was reduced in S. typhimurium-infected pigs at 24 h (P<0.01), 48 h (P<0.001), 96 h (P<0.001), and 168 h (P<0.05). Serum leptin levels were

Topics: Animals; Blotting, Western; Body Temperature; Eating; Female; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Leptin; Male; Radioimmunoassay; Salmonella Infections, Animal; Salmonella typhimurium; Swine; Swine Diseases

Certain high lean gain swine genotypes have greater sensitivity to pathogen and nonpathogen stressors evident by reduced productivity and increased mortality during disease stress or in suboptimal production environments. Saline (control) and an immunologic challenge (LPS; 25 microg lipopolysaccharide/kg BW) were administered to three genetic populations (each pig used as its own control): high lean (H), moderate lean terminal cross (MT), and moderate lean maternal cross (MM). LPS induced anorexia, and significantly increased body temperature and circulating TNF-alpha, cortisol, and NEFA in all genotypes (P < 0.0004). LPS reduced circulating glucose, insulin, and IGF-1 in all genotypes (P < 0.05). The LPS-induced hypoglycemia was significantly greater in MM versus MT and H pigs (P < 0.03). The hypoinsulinemia was significantly greater in MM versus H pigs (P < 0.02). MM pigs recovered from hypoinsulinemia slower than MT pigs (P < 0.03). Control insulin was higher in H versus MT pigs (P < 0.08), but relative to basal, the insulin response to LPS was similar. Plasma haptoglobin response to LPS was lower for MM versus MT and H pigs (P < 0.02), and tended to be lower in MT versus H pigs (P < 0.09). LPS treatment caused similar decreases in plasma IGF-1 concentrations among genotypes. Ten hours after LPS treatment, leptin mRNA abundance in adipose tissue was significantly reduced (relative to control) in MM and H pigs (P < 0.02) but not in MT pigs (P > 0.05). Physiological differences in leptin, a potent regulator of food intake and energy metabolism, may be important factors in the genetic variation in sensitivity to environmental stress.

Topics: Adipose Tissue; Animals; Blood Glucose; Colorimetry; Crosses, Genetic; Electrophoresis, Polyacrylamide Gel; Endotoxemia; Enzyme-Linked Immunosorbent Assay; Escherichia coli Infections; Fatty Acids, Nonesterified; Genotype; Hydrocortisone; Image Processing, Computer-Assisted; Insulin; Insulin-Like Growth Factor I; Leptin; Male; Nucleic Acid Hybridization; Radioimmunoassay; RNA; Swine; Swine Diseases; Tumor Necrosis Factor-alpha

The relationship between leptin mRNA and insulin status was explored using streptozotocin diabetic pigs. Twelve male Yorkshire x Landrace crossbred swine (approximately 40 kg BW) were divided into three groups. Two groups were rendered diabetic with the use of streptozotocin (75 mg/kg BW). Diabetes was confirmed 24 h after streptozotocin treatment by the presence of hyperglycemia. One group of diabetic animals received daily injections of insulin (.5 U/(kg x d)(-1)) for 7 d, whereas the other group of diabetic animals received saline injections. The nondiabetic group also received saline injections (controls). Tissue and blood were collected after 7 d of treatment. Leptin mRNA concentrations in dorsal s.c. adipose tissue were measured by Northern analysis and standardized against 28S rRNA expression. Diabetes reduced leptin mRNA concentration by 67% in s.c. adipose tissue (P < .05). Serum insulin concentrations in the diabetic animals were reduced by 69% (P < .05). Insulin treatment of diabetic animals resulted in an increase in leptin mRNA concentration to levels in controls. Primary cell culture of porcine adipose tissue was used to assess whether these actions were the direct or indirect action of insulin. Acute exposure (1 to 24 h) of primary cultures of porcine adipocytes to insulin did not result in a change in leptin expression. However, chronic (7-d) exposure to insulin elevated leptin mRNA levels by 73%. These data suggest that insulin mediates changes in porcine leptin mRNA levels in vivo or in vitro, most likely by an indirect action.

Topics: Animals; Blotting, Northern; Cells, Cultured; Diabetes Mellitus, Experimental; Insulin; Leptin; Male; RNA, Messenger; Streptozocin; Swine; Swine Diseases

Degenerate primers based on human and mouse obesity gene (OBS) sequencing data were used in the reverse transcriptase-polymerase chain reaction (RT-PCR) of total RNA from pig white adipose tissue. Both strands of the resultant pig- specific 325 bp DNA fragment were sequenced. Comparison of the obtained sequence with known sequences revealed an 86% identity with the human and 84% identity with the mouse OBS cDNA. The OBS gene was physically mapped to pig chromosome 18 by PCR analysis of somatic cell hybrids, using pig-specific primers. This result is consistent with the recent assignment of the human OBS gene to chromosome 7 and the observation made by comparative mapping that by using a human chromosome 7 specific library two segments of conserved synteny were detected on porcine chromosomes 9 and 18. We conclude the border of conserved synteny to be in the 7q31-7q32 region of the human chromosome.

Topics: Adipose Tissue; Animals; Base Sequence; Chromosome Mapping; Conserved Sequence; DNA Primers; Genetic Markers; Humans; Hybrid Cells; Leptin; Mice; Molecular Sequence Data; Obesity; Polymerase Chain Reaction; Proteins; Sequence Homology, Nucleic Acid; Swine; Swine Diseases