SNP discovery and association study for growth, fatness and meat quality traits in Iberian crossbred pigs.

Iberian pigs and its crosses are produced to obtain high-quality meat products. The objective of this work was to evaluate a wide panel of DNA markers, selected by biological and functional criteria, for association with traits related to muscle growth, fatness, meat quality and metabolism. We used 18 crossbred Iberian pigs with divergent postnatal growth patterns for whole genome sequencing and SNP discovery, with over 13 million variants being detected. We selected 1023 missense SNPs located on annotated genes and showing different allele frequencies between pigs with makerdly different growth patterns. We complemented this panel with 192 candidate SNPs obtained from literature mining and from muscle RNAseq data. The selected markers were genotyped in 480 Iberian × Duroc pigs from a commercial population, in which phenotypes were obtained, and an association study was performed for the 1005 successfully genotyped SNPs showing segregation. The results confirmed the effects of several known SNPs in candidate genes (such as LEPR, ACACA, FTO, LIPE or SCD on fatness, growth and fatty acid composition) and also disclosed interesting effects of new SNPs in less known genes such as LRIG3, DENND1B, SOWAHB, EPHX1 or NFE2L2 affecting body weight, average daily gain and adiposity at different ages, or KRT10, NLE1, KCNH2 or AHNAK affecting fatness and FA composition. The results provide a valuable basis for future implementation of marker-assisted selection strategies in swine and contribute to a better understanding of the genetic architecture of relevant traits.

The impact of prenatal environment on postnatal life and performance: Future perspectives for prevention and treatment.

The present review aims to offer a non-comprehensive outline of the current state-of-the-art and future perspectives on management and therapeutic tools for intrauterine growth restriction (IUGR) and associated prenatal programming in both human and animal species. Animals are used as models for the study of phenomena related to IUGR, but also for research on prenatal therapies with the main objective of designing and developing preventive and therapeutic strategies. The research is currently paying attention on maternal-focused pharmacological treatments and nutritional strategies but also on fetal-focused treatments. Fetal-focused treatments, administered either directly at the fetus or by using infusion of umbilical cord, amniotic sac or placenta, which avoids the administration of substances at high doses to the mother for allowing their availability at the fetoplacental level. The results obtained in this area of research using large animals (rabbits, pigs and ruminants) have a dual interest, for translational biomedicine and for veterinary medicine and animal production.

Maternal undernutrition and offspring sex determine birth-weight, postnatal development and meat characteristics in traditional swine breeds.

BACKGROUND: The aim of this study was to determine how maternal undernutrition during pregnancy and offspring birth-weight can affect the postnatal development of offspring under farm conditions, which may lead to consequences in its meat and carcass quality. The current study involved a total of 80 litters from Iberian sows fed a diet fulfilling daily requirements (n = 47; control) or providing 70% daily requirements (n = 33; underfed) from d 38 to d 90 of gestation when fetal tissue development begins. After birth, piglets born live were classified as low birth-weight (LBW; < 1 kg) and normal birth-weight (NBW; ≥1 kg). During the growing phase, 240 control and 230 underfed pigs (50% males and females) distributed by BW category and sex were studied until the slaughter. RESULTS: At birth and weaning, there were significant differences in all morphological measures and weight between NBW and LBW piglets as expected (P < 0.0005), but few effects of the gestational feed restriction. During the growing phase, NBW pigs continued with higher weight than LBW pigs on all the days of evaluation (P < 0.05), even though control-LBW-females and LBW-males showed a catch-up growth. However, underfed pigs showed slower growth and higher feed conversion ratio than control pigs (P < 0.0001) at 215 days old. Moreover, the average daily weight gain (ADWG) for the overall period was greater for NBW, male and control pigs than for their LBW, female and underfed pigs (P < 0.0001, P< 0.0005 and P< 0.05, respectively) and NBW pigs were slaughtered at a younger age than LBW pigs (P < 0.0001). After slaughtering, control pigs also had higher carcass yield and backfat depth than underfed pigs (P < 0.0005) and the maternal nutritional effect caused main changes in the polar lipid fraction of liver and loin. The fatty acid composition of loin in control pigs had higher C18:1n-9 and n-3 FA concentrations, as well as lower ∑n-6/∑n-3 ratio, than in underfed pigs (P < 0.005). CONCLUSIONS: In brief, results showed that the effects of maternal nutritional restriction appeared and increased with offspring age, causing worse developmental patterns for underfed pigs than for control pigs.

Efficiency and demographics of a high-yield dairy ewe farm with two managing systems involving five or 10 lambings per year.

This study assessed milk productivity, demographic characteristics and workload distribution on a single high-yield dairy ewe farm in Spain (Avila, Spain; continental climate, latitude of 40.90 N, altitude of 900 m) over a 7-year period considering a transition from a herd management system involving five lambings per year (5LY) to a system involving 10 lambings per year (10LY). The 5LY system was practiced on the farm from 2010 to 2012 and the 10LY system from 2014 to 2015, with 2009 and 2013 being considered transition years. During this period, 27 415 lactations were recorded from an average of 3746 Lacaune sheep/year. Several productivity parameters were higher in 2014 to 2015 than in 2010 to 2012: milk yield/lactation (370±156 v. 349±185 l), lactation length (218±75 v. 192±75 days) and dry period length (53.5±38.3 v. 69.1±34.8 days) (all P<0.0001). During 2014 to 2015, investment in new lambing facilities was possible, workload was distributed more uniformly throughout the year, workload per worker was smaller, rate of ewe culling was lower (35.39±0.53% v. 42.51±7.51%), ewe longevity was greater and higher-order lactations were more numerous (P<0.0001). On the other hand, during 2010 to 2012, daily production was higher (1.73±1.66 v. 1.70±0.62 l/day; P=0.038), the interlambing period was shorter (283±50 v. 302±44 days; P<0.0001) and lambings/ewe per year were greater (1.42±0.01 v. 1.30±0.01; P<0.05). These results suggest that a 10LY herd management system can be compatible with profitability, productivity and good animal and worker's welfare on a high-yield dairy farm, and may even be associated with better outcomes than a 5LY system.

Changes in renal hemodynamics of undernourished fetuses appear earlier than IUGR evidences.

The present study used a sheep model of intrauterine growth restriction, combining maternal undernutrition and twinning, to determine possible markers of early damage to the fetal kidney. The occurrence of early deviations in fetal hemodynamics which may be indicative of changes in blood perfusion was assessed by Doppler ultrasonography. A total of 24 sheep divided in two groups were fed with the same standard grain-based diet but fulfilling either their daily maintenance requirements for pregnancy (control group; n=12, six singleton and six twin pregnancies) or only the 50% of such quantity (food-restricted group; n=12; four singleton and eight twin pregnancies). All the fetuses were assessed by both B-mode and Doppler ultrasonography at Day 115 of pregnancy. Fetal blood supply was affected by maternal undernutrition, although there were still no evidences of brain-sparing excepting in fetuses at greatest challenge (twins in underfed pregnancies). However, there were early changes in the blood supply to the kidneys of underfed fetuses and underfed twins evidenced decreases in kidney size.

Ram semen deterioration by short-term exposure to high altitude is prevented by improvement of antioxidant status.

Ovine reproduction efficiency in herds at high altitude (ha) is lower than that at low altitude (la). In ewes, ha effects are due to hypoxia and oxidative stress. Our aim was to establish the effect of antioxidant vitamin supplementation on semen traits and antioxidant status of rams exposed to short or long time ha. A total of 32 rams native to la (~500 m) were used, 16 were kept at la and the other 16 were brought to ha (~3600 m), where they were placed in the same flock as the ha native rams (n=16). Half of the animals in each group were supplemented daily with vitamins C 600 mg and E 450 IU per os, during the entire experimental period, starting the 4th day after animal's arrival at ha (day 0). At days 0, 30 and 60 of treatment, blood and semen samples were collected for evaluation of antioxidant status and semen standard characteristics. Data were compared within each experimental time by analysis of variance using a general linear model. Elevated concentrations of oxidative stress biomarkers were present in blood from animals maintained at ha. Ejaculates from ha exposed rams showed decreased sperm concentration, progressive motility and viability, in addition to decreased antioxidant status in seminal fluid. A total of 30 days of oral supplementation with vitamins C and E prevented some ha negative effects on semen characteristics, mainly in recently ha exposed rams. It is concluded that exposure of rams to ha negatively affects semen quality, where oxidative stress plays a predominant role. These effects are mainly prevented by oral supplementation of vitamins C and E, which constitutes a simple and cheap alternative to improve semen quality of rams when they are moved to ha.

A diet supplemented with n-3 polyunsaturated fatty acids influences the metabomscic and endocrine response of rabbit does and their offspring.

The aim of the present study was to evaluate the productive, endocrine, and metabomscic responses as well as oxidative stress of rabbit does and their offspring when fed a diet supplemented with -3 PUFA during their first productive cycle. To this aim, a total of 105 rabbit does were fed ad mscibitum from d 60 to 172 of age 2 isoenergetic and isoproteic diets differing in fatty acid composition. The control diet ( = 52 does) contained 45.9 g/kg of -3 of the total fatty acids and the enriched diet ( = 53 does) contained 149.2 g/kg of -3 of the total fatty acids. Both experimental groups had similar feed intake during rearing, pregnancy, and lactation. The enrichment of diet had no effect on ultrasonographic assessment of does on d 9 and 16 of pregnancy, with an embryonic vesicle number and fetus and placenta size similar between groups ( > 0.05). Even though there were no major effects ( > 0.05) on fertimscity, duration of gestation, and number born amscive and stillborn kits at parturition, mscive kits from enriched does were longer (71.6 ± 2.42 vs. 79.5 ± 2.13 mm; < 0.05) and tended to be heavier (42.5 ± 3.94 vs. 50.8 ± 3.47 g; = 0.07) than those from control does ( < 0.05). The 2 groups had similar milk production and mortamscity values during lactation; consequently, there were no differences between diets in ADG, mscitter weight, and number of weaned kits ( > 0.05). In enriched does, higher plasma leptin and estradiol concentrations than in control does ( < 0.05) were observed. In addition, enriched females also had lower total and high-density mscipoprotein cholesterol (HDL-c) than control females during lactation ( < 0.05). Regarding offspring, the enrichment of diet with PUFA caused a hypermscipidemic status (greater values of plasma triglycerides, total cholesterol, and HDL-c; < 0.05) at 1 d postpartum (dpp), compared with the control group, that disappeared at 32 dpp. Supplemented does before parturition and their offspring at 1 dpp had greater oxidative stress than those in the control group. In conclusion, an increase of -3 PUFA concentration in the diet of rabbit does and, consequently, of their offspring during a productive cycle alters their mscipid profile and the indicators of oxidative stress, without major endocrine modifications or improvements in the productive variables.

Maternal age modulates the effects of early-pregnancy L-proline supplementation on the birth-weight of piglets.

Previous results obtained in gilts maintained under experimental conditions suggest that amino acid supplementation during pregnancy may be a promising strategy for diminishing the incidence of embryo losses and low birth-weight newborn. The current study evaluated the effects of a short-term supplementation with L-proline, around implantational stages, on litter size and birth-weight of piglets in sows of different parities maintained under commercial farm conditions. There were no significant effects in mature sows with three or more parities, but the supplementation improved the reproductive efficiency of the high-prolific first-parity sows and of all the sows at second-parity. There were numerically higher litter size (of around two more live piglets; n.s.) and higher birth-weights (P<0.05) in the supplemented animals. The results of this study indicate that the effects of L-proline supplementation on litter size and birth-weight are strongly modulated by the maternal characteristics; specifically by parity and prolificacy and that supplementation may be cost-efficient for the management of females with compromised energy balance; specifically, sows at second farrowing and highly-prolific primiparous gilts.

Fetal growth-retardation and brain-sparing by malnutrition are associated to changes in neurotransmitters profile.

The present study assesses possible changes in the levels of different neurotransmitters (catecholamines and indoleamines) in fetuses affected by nutrient shortage. Hence, we determined the concentration of catecholamines and indoleamines at the hypothalamus of 56 swine fetuses obtained at both 70 and 90days of pregnancy (n=33 and 23 fetuses, respectively). The degree of fetal development and the fetal sex affected the neurotransmitters profile at both stages. At Day 70, there were found higher mean concentrations of l-DOPA in both female and male fetuses with severe IUGR; male fetuses with severe IUGR also showed higher concentrations of TRP than normal male littermates. At Day 90 of pregnancy, the differences between sexes were more evident. There were no significant effects from either severe IUGR on the neurotransmitter profile in male fetuses. However, in the females, a lower body-weight was related to lower concentrations of l-DOPA and TRP and those female fetuses affected by severe IUGR evidenced lower HVA concentration. In conclusion, the fetal synthesis and use of neurotransmitters increase with time of pregnancy but, in case of IUGR, both catecholamines and indoleamines pathways are affected by sex-related effects.

Sex and intrauterine growth restriction modify brain neurotransmitters profile of newborn piglets.

The current study aimed to determine, using a swine model of intrauterine growth restriction (IUGR), whether short- and long-term neurological deficiencies and interactive dysfunctions of Low Birth-Weight (LBW) offspring might be related to altered pattern of neurotransmitters. Hence, we compared the quantities of different neurotransmitters (catecholamines and indoleamines), which were determined by HPLC, at brain structures related to the limbic system (hippocampus and amygdala) in 14 LBW and 10 Normal Body-Weight (NBW) newborn piglets. The results showed, firstly, significant effects of sex on the NBW newborns, with females having higher dopamine (DA) concentrations than males. The IUGR processes affected DA metabolism, with LBW piglets having lower concentrations of noradrenaline at the hippocampus and higher concentrations of the DA metabolites, homovanillic acid (HVA), at both the hippocampus and the amygdala than NBW neonates. The effects of IUGR were modulated by sex; there were no significant differences between LBW and NBW females, but LBW males had higher HVA concentration at the amygdala and higher concentration of 5-hydroxyindoleacetic acid, the serotonin metabolite, at the hippocampus than NBW males. In conclusion, the present study shows that IUGR is mainly related to changes, modulated by sex, in the concentrations of catecholamine neurotransmitters, which are related to adaptation to physical activity and to essential cognitive functions such as learning, memory, reward-motivated behavior and stress.

Developmental Origins of Health and Disease in swine: implications for animal production and biomedical research.

The concept of Developmental Origins of Health and Disease (DOHaD) addresses, from a large set of epidemiological evidences in human beings and translational studies in animal models, both the importance of genetic predisposition and the determinant role of maternal nutrition during pregnancy on adult morphomics and homeostasis. Compelling evidences suggest that both overnutrition and undernutrition may modify the intrauterine environment of the conceptus and may alter the expression of its genome and therefore its phenotype during prenatal and postnatal life. In fact, the DOHaD concept is an extreme shift in the vision of the factors conditioning adult phenotype and supposes a drastic change from a gene-centric perspective, only modified by lifestyle and nutritional strategies during juvenile development and adulthood, to a more holistic approach in which environmental, parental, and prenatal conditions are strongly determining postnatal development and homeostasis. The implications of DOHaD are profound in all the mammalian species and the present review summarizes current knowledge on causes and consequences of DOHaD in pigs, both for meat production and as a well-recognized model for biomedicine research.

Characterization of early changes in fetoplacental hemodynamics in a diet-induced rabbit model of IUGR.

Intrauterine growth restriction (IUGR) is associated with adverse perinatal outcomes and late-onset diseases in offspring. Eating disorders, voluntary caloric restriction and maternal undernutrition can all induce IUGR but a relevant model is required to measure all its possible consequences. In this work, pregnant rabbits were used as an IUGR model. Control females (n=4) received ad libitum diet throughout pregnancy, whereas underfed females (n=5) were restricted to 50% of their daily requirements. Offspring size was measured by ultrasonography and in vivo at birth. Hemodynamic features of the umbilical cords and middle cerebral arteries (systolic peak velocity, end diastolic velocity, pulsatility index and resistance index) were characterized by Doppler ultrasonography. At day 21, maternal underfeeding resulted in a significant reduction of fetal size (occipito-nasal length). At birth, the size of kits from the underfed group was significantly lower (lower crown-rump length, biparietal and transversal thoracic diameters) and a reduced weight with respect to the control group. Feed restriction altered blood flow perfusion compared with does fed ad libitum (significant higher systolic peak, time-averaged mean velocities and lower end diastolic velocity). Fetuses affected by IUGR presented with compensative brain-sparing effects when compared with the control group. In conclusion, the present study supports using rabbits and the underfeeding approach as a valuable model for IUGR studies. These results may help to characterize IUGR alterations due to nutrient restriction of mothers in future research.

Preselection of high and low ovulatory responders in sheep multiple ovulation and embryo transfer programs.

The present study evaluated the feasibility of carrying out an easy-to-handle and cost-efficient test for the preselection of high- and low-ovulatory responder ewes under superovulatory protocols. The test was based on the assessment of the number of ovulations obtained in response to the administration of a single-shot eCG treatment. The predictive value of the test was determined by comparing the number of ovulations with yields obtained in response to a multiple-dose FSH treatment. In addition, the study determined possible effects of follicular status at first FSH dose and their relationship with subsequent ovarian response. A total of 31 Merino ewes received hormonal treatment comprising the administration of 800 IU of eCG at the end of progestative treatment. Twenty-three days later, multiple-dose FSH treatment (80-mg FSH, in six decreasing doses between Days 12 and 14 of a second progestative treatment) was applied to the same ewes. The study showed a significant relationship between the number of corpora lutea obtained in response to eCG treatment with respect to those obtained in response to FSH treatment (r = 0.791; P < 0.05), which resulted in 84% recurrence rate. The number of embryos was greater for high-responder in relation to low-responder ewes (7.2 ± 3.7 and 4.0 ± 3.9, respectively; P < 0.05), whereas rates of recovery and fertilization were similar between groups (P > 0.05). Hence, there was a tendency for a higher mean of grades 1 and 2 embryos in high-responder in relation to low-responder ewes (6.1 ± 3.8 and 3.7 ± 4.0, respectively; P < 0.1). No significant relationship was found between the number of corpora lutea in response to FSH treatment and the number of small and total follicles at first FSH dose (P > 0.05). However, a negative low relationship was found between the presence of large follicles and the ovulation rate in response to FSH treatment (r = -0.361; P < 0.05). In conclusion, the results show the feasibility of carrying out an easy-to-handle and cost-efficient procedure for the preselection of embryo donors. The procedure was based on high recurrence rate between hormonal treatments, which in turn accounts for a distinctive ewe ovulatory response.

Dietary vitamin A restriction affects adipocyte differentiation and fatty acid composition of intramuscular fat in Iberian pigs.

The aim of this study was to investigate whether dietary vitamin A level is associated with differences in adipocyte differentiation or lipid accumulation in Iberian pigs at early growing (35.8kg live weight) and at finishing (158kg live weight). Iberian pigs of 16.3kg live weight were allocated to two feeding groups, one group received 10,000IU of vitamin A/kg diet (control); the other group received a diet with 0IU of vitamin A (var) for the whole experimental period. The dietary vitamin A level had no effect on growth performance and carcass traits. The early suppression of vitamin A increased the preadipocyte number in Longissimus thoracis (LT) muscle in the early growth period (P<0.001) and the neutral lipid content and composition (higher MUFA and lower SFA content) at the end of the finishing period (P<0.05). Vitamin A restriction in young pigs increases their lipogenic potential without affecting carcass traits.

IFPA meeting 2014 workshop report: Animal models to study pregnancy pathologies; new approaches to study human placental exposure to xenobiotics; biomarkers of pregnancy pathologies; placental genetics and epigenetics; the placenta and stillbirth and fetal growth restriction.

Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2014 there were six themed workshops, five of which are summarized in this report. These workshops related to various aspects of placental biology but collectively covered areas of animal models, xenobiotics, pathological biomarkers, genetics and epigenetics, and stillbirth and fetal growth restriction.

Alternative method for intramuscular fat analysis using common laboratory equipment.

A procedure to quantify intramuscular fat was developed using common inexpensive laboratory equipment. Three homogenization methods of lyophilized muscle samples (Ball-mill, Grinder and Mortar) and two extraction methods (Ball-mill or Vortex) were used in turkey meat and pork. Two-hundred mg of lyophilized and homogenized samples were accurately weighed and mixed with 1.5 mL of dichloromethane-methanol (8:2) and shaken either in a Mixer Mill (MM400, Retsch Technology) or in a Vortex. The final mixture was separated by centrifugation. Solvent was evaporated under a nitrogen stream and lipid content was gravimetrically determined. Besides, it was checked that the fatty acid profile was not altered by the protocol used. Moreover, the analysis of 4 replicas from the same sample showed different variation coefficients (16-29%) for the new procedures proposed over a wide range of IMF content. The combination of Grinder and Vortex methodologies can be proposed as a simple and inexpensive alternative to previous ones.

Fertility of a high-altitude sheep model is compromised by deficiencies in both preovulatory follicle development and plasma LH availability.

At high altitude, hypoxia and/or oxidative stress may compromise fertility. This study tested the relative effect of short- or long-term exposure to high-altitude hypobaric hypoxia and oxidative stress in sheep on preovulatory follicle dynamics and gonadotrophin secretion. Thus, growth dynamics, stereidogenic function and competence to ovulate of preovulatory follicles, as well as FSH and LH availability throughout the entire oestrous cycle, were compared among sheep native from low and high altitude, and sheep newcomers to high altitude. The results indicates that short-term exposure in sheep newcomers to high altitude has a deleterious effect on both the ovarian function (affecting preovulatory follicular development) and the pituitary function (diminishing plasma LH availability). On the other hand, there were no detected differences in the preovulatory follicular development in sheep adapted to high altitude for generations and, conversely, LH secretion was increased, which suggests an adaptive mechanism. The treatment with antioxidant agents during a relative short period for the time of folliculogenesis (approximately 1 month and a half) changed substantially the development of preovulatory follicles in short-term exposed sheep to similar patterns than in sheep native and living to both high and low altitude. These results highlight the role of oxidative stress in the detriment of the reproductive function in individuals recently exposed to high-altitude hypoxic environment.

Maternal aging affects life performance of progeny in a Holstein dairy cow model.

The development and life performance of 404 high-producing Holstein dairy cows was studied from birth onwards and during two lactations. The management, environment and parental genetics of the cows were known in detail. Cluster analysis identified four performance 'types': high-yielding (HY) cows and persistently high-yielding (PHY) cows, which accounted for 33% of the animals; medium-yielding (MY) cows, 41%; and low-yielding (LY) cows, 26%. Prenatal determinants of the life performance of the progeny were analyzed. Developmental and environmental factors were excluded as determinants of performance (including birth weight, level of passive immunity transfer, growth rate, age at first parturition and reproductive efficiency). Life performance did show minor seasonal effects, with more HY cows but less PHY being born during the cold season (90.1% in HY; 58.3% in PHY v. 81.5%). Instead, the single most important factor influencing life performance of daughters was maternal age. HY cows were born from the youngest mothers (1.89±1.14 parturitions, 3.12±1.42-year old), whereas LY cows were born from the oldest (2.72±1.80 parturitions, 3.97±2.01-year old; P<0.001). Life performance of the dams did not differ among clusters. In addition, metabolic parameters (fat and protein yield) were found to correlate significantly with yields between the first and second lactations (milk yield: r=0.357; fat yield: r=0.211; protein yield: r=0.277; P<0.0001), suggesting the influence of the individual. These results suggest that under optimal health, nutritional and environmental conditions, maternal aging is an important determinant of the life performance of progeny and argue for the need to identify conditions that contribute to health and disease in progeny according to the Developmental Origin of Health and Disease or DOHaD concept. Our findings may help the development of novel management guidelines for dairy farms.

Advanced onset of puberty after metformin therapy in swine with thrifty genotype.

The prevention and treatment of obesity in children is based on adequate nutrition and exercise plus antihyperglycaemic drugs. Currently, the incidence of childhood obesity is aggravated in ethnicities with thrifty genotype, but there is no available information on the effects of metformin therapy. The relative effects of lifestyle and metformin on patterns of growth, fattening, metabolic status and attainment of puberty were assessed in females of an obese swine model (Iberian gilts), allocated to three experimental groups (group A, obesogenic diet and scarce exercise; group DE, adequate diet and opportunity for exercise; and group DEM, adequate diet and opportunity for exercise plus metformin). Group A evidenced high weight, corpulence and adiposity, high plasma triglycerides and impairments of glucose regulation predisposing to insulin resistance. These features were favourably modulated by adequate lifestyle (group DE), and these effects were strengthened by metformin treatment (group DEM), which induced an improvement in body development by favouring muscle deposition. However, contrary to expectations, metformin advanced the onset of puberty. Metformin treatments would have positive effects on growth patterns, adiposity and metabolic features of young females from ethnicities with thrifty genotype or developing leptin resistance, but a negative effect by advancing the attainment of puberty. This study provides a warning regarding the use of metformin, without further studies, in girls from these ethnicities.

Prenatal programming of obesity in a swine model of leptin resistance: modulatory effects of controlled postnatal nutrition and exercise.

The main role of early nutritional programming in the current rise of obesity and associated diseases is well known. However, translational studies are mostly based in postnatal food excess and, thus, there is a paucity of information on the phenotype of individuals with prenatal deficiencies but adequate postnatal conditions. Thus, we assessed the effects of prenatal programming (comparing descendants from females fed with a diet fulfilling 100 or only 50% of their nutritional requirements for pregnancy) on gene expression, patterns of growth and fattening, metabolic status and puberty attainment of a swine model of obesity/leptin resistance with controlled postnatal nutrition and opportunity of exercise. Maternal restriction was related to changes in the relationships among gene expression of positive (insulin-like growth factors 1 and 2) and negative (myostatin) regulators of muscle growth, with negative correlations in gilts from restricted pregnancies and positive relationships in the control group. In spite of these differences, the patterns of growth and fattening and the metabolic features during juvenile growth were similar in control gilts and gilts from restricted pregnancies. Concomitantly, there was a lack of differences in the timing of puberty attainment. However, after reaching puberty and adulthood, females from restricted pregnancies were heavier and more corpulent than control gilts, though such increases in weight and size were not accompanied by increases in adiposity. In conclusion, in spite of changes in gene expression induced by developmental programming, the propensity for higher weight and adiposity of individuals exposed to prenatal malnutrition may be modulated by controlled food intake and opportunity of physical exercise during infant and juvenile development.