Small Litters Research Articles

Some mechanisms underlying variation in vital rates of grizzly bears on a multiple use landscape

Understanding factors that govern the abundance of organisms is fundamental to the science of ecology and important for conservation and management of species. I used temporal and spatial comparisons to test the influence of human industrial activity, huckleberry (Vaccinium membranaceum) productivity, and population density on grizzly bear (Ursus arctos) vital rates and population trends over a 32-year period. Survival rates of adult and subadult males were 0.84 and 0.78, respectively, and lower than those of adult (0.93) or subadult females (0.96). Of the 31 bears that died while radio-collared, 26 (84%) were killed by people. Of those killed by people, 11 (35%) were legally killed by hunters and 84% were deaths that occurred <120 m from a road. In the first decade of study (1979–1988) when salvage logging and gas exploration was intensive, bear density was relatively low, and huckleberry production was generally good, the population increased (λ = 1.074) with high survival rates of cubs (0.84) and yearlings (0.86) plus a high reproductive rate of 0.374. During the second decade (1989–1998) when there was little industrial activity and huckleberry production remained good, the population continued to grow (λ ≈ 1.06–1.08) because survival of all age classes remained high, but the reproductive rate declined to 0.257. Bear density reached its maximum (55.6 bears/1,000 km2 excluding independent males) at the start of the third decade. During the third decade (1999–2010), there was little industrial activity, but huckleberry production declined dramatically and often completely failed. During the third decade the population declined (λ ≈ 0.955–0.980) as the reproductive rate dropped to 0.192 because of small litters (1.82), extended interbirth intervals (2.93, 3.44, and 4.22 years in decades 1, 2, and 3, respectively) and increased age of primiparity (6.60, 7.09, and 10.46 years in decades 1, 2, and 3, respectively). Adult female survival also declined likely because more females were without offspring and thus vulnerable to hunting. The best model predicting if a parous female would have a small (0 or 1 cub) or large (2 or 3 cub) litter when not encumbered with offspring the previous mating season included both huckleberry abundance the previous year and female bear density. Population inventories during the third decade had approximately twice as many bears detected per DNA hair trap set in the portion of the valley where there had been rapid industrial development, grizzly bear hunting, and large huckleberry fields than in an adjacent portion of the valley that was protected from industry and hunting but with no major huckleberry fields. The abundance of huckleberries growing in mountains above most human activity permitted this population to expand in spite of the industrial development. The population was primarily regulated by the interaction of bear density and the density-independent production of huckleberries, their major summer-fall energy food. © 2015 The Wildlife Society.

Metabolic and Gonadotropic Impact of Sequential Obesogenic Insults in the Female: Influence of the Loss of Ovarian Secretion.

The reproductive impact of persistent energy excess in the female remains incompletely defined, yet the escalating prevalence of obesity calls for better understanding of this phenomenon. Also along this line, the influence of ovarian hormones on the pathophysiology of obesity and its comorbidities merits further investigation. We study here the metabolic and gonadotropic impact of sequential obesogenic insults, namely postnatal overnutrition [by rearing in small litters (SL)] and high-fat diet (HFD) after weaning, in gonadal-intact and ovariectomized (OVX) female rats. In young (4 mo) females, SL or HFD similarly increased body weight, yet only a HFD evoked additional metabolic perturbations, some of which were worsened by precedent SL. In addition, HFD concomitantly decreased LH and estradiol levels and, when combined with SL, suppressed Kiss1 expression in the hypothalamic arcuate nucleus in 4-month females, whereas HFD up to 10-month also reduced LH responses to kisspeptin-10. OVX caused rapid deterioration of the metabolic profile, with overweight, increased energy intake, and deregulation of leptin and glucose/insulin levels, effects whose magnitude was similar to, if not higher than, HFD. Summation of previous obesogenic insults maximally increased body weight, basal leptin, insulin and glucose levels, and glucose intolerance. Yet OVX obliterated the inhibitory effects of overweight/HFD on gonadotropin levels and arcuate nucleus Kiss1 expression. Our study documents the deleterious consequences of sequential obesogenic insults on the female gonadotropin axis, which involve central impairment of the Kiss1 system. In addition, our work delineates the dramatic impact of the loss of ovarian secretions, as the menopausal model, on the metabolic profile of female rats, especially when combined with preceding obesogenic challenges.

Perinatal overnutrition exacerbates adipose tissue inflammation caused by high-fat feeding in C57BL/6J mice.

Obesity causes white adipose tissue (WAT) inflammation and insulin resistance in some, but not all individuals. Here, we used a mouse model of early postnatal overfeeding to determine the role of neonatal nutrition in lifelong WAT inflammation and metabolic dysfunction. C57BL/6J mice were reared in small litters of 3 (SL) or normal litters of 7 pups (NL) and fed either regular chow or a 60% high fat diet (HFD) from 5 to 17 weeks. At weaning, SL mice did not develop WAT inflammation despite increased fat mass, although there was an up-regulation of WAT Arg1 and Tlr4 expression. On HFD, adult SL mice had greater inguinal fat mass compared to NL mice, however both groups showed similar increases in visceral fat depots and adipocyte hypertrophy. Despite the similar levels of visceral adiposity, SL-HFD mice displayed greater impairments in glucose homeostasis and more pronounced hepatic steatosis compared to NL-HFD mice. In addition, WAT from SL mice fed a HFD displayed greater crown-like structure formation, increased M1 macrophages, and higher cytokine gene expression. Together, these data suggest that early postnatal overnutrition may be a critical determinant of fatty liver and insulin resistance in obese adults by programming the inflammatory capacity of adipose tissue.

0131 : Impact of overweight on anthracycline and trastuzumab-induced cardiotoxicity: experimental study in mice

Trastuzumab (TRZ), a humanized monoclonal antibody against Human Epidermal Growth Factor Receptor 2 (HER2) oncogene, is believed to potentiate doxorubicin (DOX) cardiotoxicity, resulting in left ventricular dysfunction. Few data indicate that overweight could influence DOX-induced cardiotoxicity, and no study has already evaluated the impact of moderate overweight on the cardiotoxic effect of DOX alone or in combination with TRZ. Immediately after birth, litters of C57BL/6 mice were either maintained at 10 (normal litter, NL), or reduced to 3 (small litter, SL) in order to induce programming of ~15% overweight through postnatal overfeeding. At 4 months, in order to evaluate the potentiation of DOX cardiotoxicity by TRZ, NL and SL mice received a single intraperitoneal injection of either saline, DOX (6mg/kg), TRZ (10mg/kg) or the combination of both (DOX-TRZ). Transthoracic echocardiography was performed 24 hours before, 10 and 20 days after treatments, in order to evaluate the evolution of cardiac function. Twenty days after DOX administration, systolic dysfunction was observed only in overweight-SL group, while NL mice group kept a preserved left ventricular ejection fraction (LVEF). Moreover, in NL group, the function impairment appeared when TRZ was co-administrated. 48 hours after drug administration, gene expression of Erb-B2, the murine analog of HER2, was induced in the myocardium of DOX-treated mice, and its induction was potentiated by co-treatment with TRZ. Expression of natriuretic peptides (ANP, BNP) appeared to be potentiated in DOX-TRZ mice of both NL and SL groups, whereas the expression of b-MHC increased significantly in overweight- SL mice. In an acute model of DOX cardiotoxicity, moderately overweighed adult mice are more sensitive to cardiac systolic impairment. Moreover, our results show an early myocardial induction of TRZ-receptor after DOX and/or TRZ, and confirm the potentiating action of TRZ on DOX-induced cardiotoxicity in mice

Cascading effects of habitat on maternal condition and life-history characteristics of neonatal mule deer

The condition of maternal female mammals greatly influences life-history characteristics of their young, but interactions between habitat and maternal condition and their combined influences on birth characteristics and survival of neonates are less well understood, especially in free-ranging populations. We monitored survival of neonatal mule deer (Odocoileus hemionus) inhabiting 2 contrasting ecotypes in Idaho: aspen woodlands (Populus tremuloides) in southeast Idaho (Caribou Mountains) and mixed-conifer grasslands (lodge-pole pine, Pinus contorta; Douglas-fir, Pseudotsuga menziesii) in central Idaho (Salmon River Mountains). We expected the Caribou Mountains to offer better forage and greater concealment cover than the Salmon River Mountains. We tested for an array of maternal influences on neonatal deer inhabiting those dissimilar ecosystems. We monitored 96 neonates from date of capture to 5 months of age (n = 44 in the Caribou Mountains, 2010; n = 52 in the Salmon River Mountains, 2011). Survival and birth characteristics consistently diverged between study areas, whereas timing of births was similar. Female deer from the Salmon River Mountains exhibited poor maternal condition and small litter sizes compared with females from the Caribou Mountains. Young from the Salmon River Mountains exhibited lower rates of growth, occupied bedding sites with less concealment cover, and subsequently experienced lower survival from birth to 5 months of age, compared with neonates from the Caribou Mountains. Cause of deaths for young mule deer on both study sites was mostly from predation. Our findings emphasize the potential role that habitat plays in the population dynamics of mule deer via cascading effects on physical condition, reproduction, and survival. Changes in habitat, potentially associated with changing climate, fire regimes, and land uses, probably have contributed to the widespread declines in populations of mule deer during recent decades.

Strong stoichiometric resilience after litter manipulation experiments; a case study in a Chinese grassland

Abstract. Global climate change has generally modified net primary production (NPP) which leads to increasing litter inputs in some ecosystems. Therefore, assessing the impacts of increasing litter inputs on soil nutrients, plant growth and ecological carbon (C) : nitrogen (N) : phosphorus (P) stoichiometry is critical for an understanding of C, N and P cycling and their feedback processes to climate change. In this study, we added plant above-ground litter, harvested near the experimental plots, to the 10–20 cm subsoil layer of a steppe community at rates equivalent to annual litter input of 0, 15, 30, 60 and 120%, respectively, covering the entire range of the expected NPP increases in this region due to climate change (10–60%). We measured the resulting C, N and P content of different pools (above- and below-ground plant biomass, litter, microbial biomass). Small litter additions, which are more plausible compared to the expected increase predicted by Earth system models, had no effect on the variables examined. Nevertheless, high litter addition (120% of the annual litter inputs) significantly increased soil inorganic N and available P, above-ground biomass, below-ground biomass and litter. Our results suggest that while very high litter addition can strongly affect C : N : P stoichiometry, the grassland studied here is resilient to more plausible inputs in terms of stoichiometric functioning.

Swimming training prevents metabolic imprinting induced by hypernutrition during lactation

Reduction in litter size during lactation induces hypernutrition of the offspring culminating with altered metabolic programming during adult life. Overnourished rats present alterations in the endocrine pancreas and major predisposition to the development of type 2 diabetes. Our study evaluated the impact of swimming training on insulin secretion control in overnourished rats. At postnatal day 3 male rat pup litters were redistributed randomly into Small Litters (SL, 3 pups) or Normal Litters (NL, 9 pups) to induce early overfeeding during lactation. Both groups were subjected to swimming training (3 times/week/30min) post-weaning (21 days) for 72 days. At 92 days of life pancreatic islets were isolated using collagenase technique and incubated with glucose in the presence or absence of acetylcholine (Ach, 0.1-1000μM) or glucagon-like peptide 1 (GLP1, 10nM). Adipose tissue depots (white and brown) and endocrine pancreas samples were examined by histological analysis. Food intake and body weight were measured. Blood biochemical parameters were also evaluated. Swimming training prevented metabolic program alteration by hypernutrition during lactation. Exercise reduced obesity and hyperglycemia in overnourished rats. Pancreatic islets isolated from overnourished rats showed a reduction in glucose-induced insulin secretion and cholinergic responses while the insulinotropic action of GLP1 was increased. Physical training effectively restored glucose-induced insulin secretion and GLP1-stimulated action in pancreatic islets from overnourished rats. However, swimming training did not correct the weak cholinergic response in pancreatic islets isolated from overnourished rats. Swimming training avoids obesity development, corrects glucose-induced insulin secretion, as well as, GLP1 insulinotropic response in overnourished rats.

Neonatal overfeeding attenuates acute central pro-inflammatory effects of short-term high fat diet.

Neonatal obesity predisposes individuals to obesity throughout life. In rats, neonatal overfeeding also leads to early accelerated weight gain that persists into adulthood. The phenotype is associated with dysfunction in a number of systems including paraventricular nucleus of the hypothalamus (PVN) responses to psychological and immune stressors. However, in many cases weight gain in neonatally overfed rats stabilizes in early adulthood so the animal does not become more obese as it ages. Here we examined if neonatal overfeeding by suckling rats in small litters predisposes them to exacerbated metabolic and central inflammatory disturbances if they are also given a high fat diet in later life. In adulthood we gave the rats normal chow, 3 days, or 3 weeks high fat diet (45% kcal from fat) and measured peripheral indices of metabolic disturbance. We also investigated hypothalamic microglial changes, as an index of central inflammation, as well as PVN responses to lipopolysaccharide (LPS). Surprisingly, neonatal overfeeding did not predispose rats to the metabolic effects of a high fat diet. Weight changes and glucose metabolism were unaffected by the early life experience. However, short term (3 day) high fat diet was associated with more microglia in the hypothalamus and a markedly exacerbated PVN response to LPS in control rats; effects not seen in the neonatally overfed. Our findings indicate neonatally overfed animals are not more susceptible to the adverse metabolic effects of a short-term high fat diet but may be less able to respond to the central effects.

Increased prepubertal body weight enhances leptin sensitivity in proopiomelanocortin and neuropeptide y neurons before puberty onset in female rats.

Pubertal onset may be advanced by obesity, with leptin potentially acting as a permissive factor. We hypothesized that having increased body weight (BW) prepubertally affects the ability of leptin to activate intracellular signaling pathways and modulate the expression of hypothalamic neuropeptides involved in reproduction and metabolism. Because being raised in small litters (SLs) tends to increase BW at weaning, female rats were raised in litters of 4 or large litters (LLs) of 12 pups. Leptin (3 μg/g BW) or vehicle (saline) was injected sc at postnatal day (PND) 21 and 30. Rats raised in SLs weighed more at both ages, but relative visceral and subcutaneous fat was increased only on PND21. Serum leptin levels were not different at PND21 or PND30. At PND21, key elements of intracellular leptin signaling (phosphorylated signal transducer and activator of transcription 3 and phosphorylated Akt [p-Akt]) were lower in SL than in LL rats. Leptin injection stimulated phosphorylated signal transducer and activator of transcription 3 in both groups, with a greater increase in LL, whereas p-Akt rose only in SL rats. At PND30, basal leptin signaling did not differ between LL and SL rats. Leptin activation of Akt was similar at 45 minutes, but at 2 hours p-AKT levels were higher in SL than in LL rats, as was the decrease in neuropeptide Y mRNA and increase in pro-opiomelanocortin mRNA levels. No change in the reproductive axis was found. Thus, being raised in SLs increases BW and visceral body fat content, fails to increase plasma leptin concentrations, and increases the leptin responsiveness of both neuropeptide Y and pro-opiomelanocortin cells in the prepubertal hypothalamus.

Do mothers prefer helpers or smaller litters? Birth sex ratio and litter size adjustment in cotton-top tamarins (Saguinus oedipus).

Sex allocation theory has been a remarkably productive field in behavioral ecology with empirical evidence regularly supporting quantitative theoretical predictions. Across mammals in general and primates in particular, however, support for the various hypotheses has been more equivocal. Population-level sex ratio biases have often been interpreted as supportive, but evidence for small-scale facultative adjustment has rarely been found. The helper repayment (HR) also named the local resource enhancement (LRE) hypothesis predicts that, in cooperatively breeding species, mothers invest more in the sex which assists with rearing future offspring and that this bias will be more pronounced in mothers who require extra assistance (i.e., due to inexperience or a lack of available alloparents). We tested these hypotheses in captive cotton-top tamarins (Saguinus oedipus) utilizing the international studbook and birth records obtained through a questionnaire from ISIS-registered institutions. Infant sex, litter size, mother's age, parity, and group composition (presence of nonreproductive subordinate males and females) were determined from these records. The HR hypothesis was supported over the entire population, which was significantly biased toward males (the “helpful” sex). We found little support for helper repayment at the individual level, as primiparous females and those in groups without alloparents did not exhibit more extreme tendencies to produce male infants. Primiparous females were, however, more likely to produce singleton litters. Singleton births were more likely to be male, which suggests that there may be an interaction between litter size adjustment and sex allocation. This may be interpreted as supportive of the HR hypothesis, but alternative explanations at both the proximate and ultimate levels are possible. These possibilities warrant further consideration when attempting to understand the ambiguous results of primate sex ratio studies so far.

Contribution of Suckling Stimulation to the Daily Periodic Display of Nursing Behavior in Non-Lactating Virgin Rabbits

A female rabbit (does) nurse once a day for three min with circadian periodicity. This timing is controlled by the amount of suckling stimulation received as small litters (2-4 kits) disrupt nursing periodicity and increase the duration of nursing bouts. Yet, as suckling induces: a) the secretion of oxytocin and prolactin and b) milk ejection, the relative contribution of those two types of factors to the daily timing of nursing needs to be independently explored. Therefore, the objective of the present work was to determine the relevance of milk output for the circadian display of rabbit nursing behavior. Methods: We used the model of anosmic virgins, as they can be induced to behave maternally (by lesioning the olfactory epithelium), they allow suckling from (foster) kits, but they are unable to produce milk. Does were given five foster kits, aged 1-5 days, placed inside a transparent nest box within the maternal cage, and replaced daily. The does' behavior was recorded continuously for 15 days through a video system allowing us full view of the animals. Results: By day 6 post-lesion 70% of virgins (i.e., 14/20) were entering the nest box, adopting a crouching posture over the litter, allowing suckling, and leaving ca. 3 min. later. 55% (i.e., 11/20) of lesioned virgins displayed nursing behavior with a ca. 24 hr periodicity, as determined by a Rayleigh analysis (3 does) or a linear regression (8 does). Conclusions: a) daily periodicity of nursing behavior can occur regardless of milk output or a preceding pregnancy; b) such factors, however, contribute to the display of a single daily episode of circadian nursing behavior in most does.

Experimental evidence that litter size imposes an oxidative challenge to offspring.

The post-natal environment in which young develop can substantially impact development, adult phenotype and fitness. In wild mice, competition among litter-mates affects development rate and adult behaviour. We manipulated post-natal litter size in a cross-fostering design to investigate the effects of enlarged and reduced litter sizes on sexual signalling, oxidative stress and the links between them. Oxidative stress causes somatic damage that can limit reproductive success and lifespan, and is predicted to mediate investment in life-history traits, including sexual signals. We predicted that litter enlargement would cause an increase in potential oxidative stress, inhibit growth and reduce sexual signalling in male mice. Males reared in enlarged litters were smaller at weaning and, despite rapid growth immediately after weaning, remained smaller at 10 weeks of age than those reared in smaller litters. Females from enlarged litters were consistently smaller throughout post-weaning development and showed no increase in growth rate compared with females from reduced litters. In enlarged litters, protein thiol concentration was lower at weaning in the liver and kidneys, with this trend continuing at 10 weeks of age in the kidneys only. Aconitase enzyme activity was also lower in mice from enlarged litters at weaning and 10 weeks of age in the kidneys. Male mice from enlarged litters scent marked more frequently and had larger preputial glands than those from reduced litters, indicating greater sexual signalling investment irrespective of this increased oxidative challenge. The results of this study are the first to reveal oxidative costs of developmental stress in small mammals.

Growth performance of genetically modified tilapia (Oreochromis niloticus) cultured in concrete pond

Reproductive data from 24 does (Chinchilla X New Zealand White) of twenty weeks, were analyzed to determine the effect of generation, housing systems and season on the reproductive performance of rabbits raised in the humid tropics. The experiment was carried out during four seasons namely: early dry season (EDS-September to November), late dry season (LDS- December to February), early rainy season (ERS-March to May) and late rainy season (LRS June to August). The study was repeated in the second generation and the data obtained were subjected to analysis of variance in a 2x2x4 factorial arrangement. Factors considered were generations, housing systems, and seasons respectively. Highest breeding efficiency of 83.33% was obtained in the first generation and maximum litter size at birth (35) and weaning (28) were observed in caged-does that kindled in EDS of first and second generations respectively, while does housed on deep litter system produced the smallest litter size at birth (24) and weaning (18) in the ERS of the second generation. Highest (12) and least (4) pre-weaning losses were recorded in caged-does that kindled in ERS of the first and second generation respectively, whereas highest average birth weight (120.58g) was observed in litters of deep litter-does that kindled in EDS of the second generation. These results indicated that the production of rabbits for breeding purposes is better achieved during early dry season (September-November) and also revealed that deep litter system allows satisfactory performance and has comparative advantage over wooden cage system considering the reduction in housing cost and can be used to improve the nutritional status of the family and also to obtain some supplementary income. Keywords: Season, Breeding efficiency, Litter size, Cage, Deep litter

Heterosis and genetic variation in the litter size of purebred and crossbred mink.

Crosses between different mink lines from 3 Danish mink farms that use different breeding strategies were studied to estimate heterosis and variance components for litter size. The study was designed to analyze crosses between lines of the same color type, between different color types, and between animals originating from different farms. Effect of heterosis, color type, and variance components were estimated using Average information REML (AI-REML) algorithm implemented in the DMU package for analyzing multivariate mixed models. Females from 7 generations that gave birth to at least 1 offspring were analyzed and the effects of parity and production year were included in the analyses. Genetic trend and the proportions of the total variance explained by the effects of additive genetics (h2), common environment (due to repeated litters from the same female; c2), and dam of the female (granddame of the born litter; d2) were estimated. The results showed that mink of the Black color type potentially produced smaller litters compared to mink of the other studied color types. We found significant general maternal effect of heterosis for litter size. Analyses of specific heterosis showed a significant positive effect of crossing between lines of the same color type. Estimates of variance components revealed h2 levels for farm A, B, and C of 0.15, 0.06, and 0.09, respectively; thus litter size could be selected for in the future. The effect of common environment on litter size was also considerable, with c2 values of 0.005, 0.11, and 0.15 at farms A, B, and C, respectively. In conclusion, we recommend genetic selection as a means of increasing litter size in farmed mink.

Community attributes determine facilitation potential in a semi-arid steppe

a b s t r a c t Studies on positive plant-plant relations have traditionally focused on pair-wise interactions. Conversely, the interaction with other co-occurring species has scarcely been addressed, despite the fact that the entire community may affect plant performance. We used woody vegetation patches as models to eval- uate community facilitation in semi-arid steppes. We characterized biotic and physical attributes of 53 woody patches (patch size, litter accumulation, canopy density, vegetation cover, species number and identity, and phylogenetic distance), and soil fertility (organic C and total N), and evaluated their relative importance for the performance of seedlings of Pistacia lentiscus, a keystone woody species in western Mediterranean steppes. Seedlings were planted underneath the patches, and on their northern and south- ern edges. Woody patches positively affected seedling survival but not seedling growth. Soil fertility was higher underneath the patches than elsewhere. Physical and biotic attributes of woody patches affected seedling survival, but these effects depended on microsite conditions. The composition of the community of small shrubs and perennial grasses growing underneath the patches controlled seedling performance. An increase in Stipa tenacissima and a decrease in Brachypodium retusum increased the probability of survival. The cover of these species and other small shrubs, litter depth and community phylogenetic dis- tance, were also related to seedling survival. Seedlings planted on the northern edge of the patches were mostly affected by attributes of the biotic community. These traits were of lesser importance in seedlings planted underneath and in the southern edge of patches, suggesting that constraints to seedling estab- lishment differed within the patches. Our study highlights the importance of taking into consideration community attributes over pair-wise interactions when evaluating the outcome of ecological interac- tions in multi-specific communities, as they have profound implications in the composition, function and management of semi-arid steppes.

Sex differences in gut satiety hormones peptide-YY and glucagon-like peptide-1 in pups raised in larger lactation litter sizes

Introduction: Previous studies have established that the size of litters during lactation influences body size and adiposity in male rat pups. Levels of gut hormones such as appetite-stimulating ghrelin and appetite-reducing peptide-YY (PYY) and glucagon-like peptide-1 (GLP-1) have not been examined in this model despite an increased susceptibility to obesity into adulthood. This study aimed to establish whether changes in gut appetite hormones, resulting from lactation litter size, could contribute to the increased risk of adulthood obesity. Methods: Male and female littermates from small (n=4), control (n=8) and large (n=12) litter sizes were studied at weaning age (25 days), with litter sizes adjusted prior to 1 day postpartum; pups remained with the dams throughout the study. Stomach ghrelin and colonic PYY and GLP-1 were quantified using radioimmunoassay. Stomachs were emptied, blotted dry and weighed. Body length was taken from between the front paws to the anus. Results and Discussion: No differences were found in stomach ghrelin levels between the pups, but levels of the gut satiety hormones PYY and GLP-1 were found to be altered in colon tissue. In descending colon, PYY and GLP-1 concentrations were significantly lower in male, but not female, pups from the large litters. Physically, both the male and female pups fed in the large litters were significantly shorter and lighter and had significantly lighter stomach tissue. We suggest that the significantly smaller male pups may have had reduced satiety as a mechanism to achieve ‘catch-up growth’ into adulthood. It is unclear whether females may show similar adaptations at a later stage. This study further demonstrated differences between young males and females, with differences evident even before sexual maturation. This work highlights the importance of standardising litter size as early as possible, especially in studies of appetite control.

Neonatal overnutrition causes early alterations in the central response to peripheral ghrelin.

ObjectiveExcess nutrient supply and rapid weight gain during early life are risk factors for the development of obesity during adulthood. This metabolic malprogramming may be mediated by endocrine disturbances during critical periods of development. Ghrelin is a metabolic hormone secreted from the stomach that acts centrally to promote feeding behavior by binding to growth hormone secretagogue receptors in the arcuate nucleus of the hypothalamus. Here, we examined whether neonatal overnutrition causes changes in the ghrelin system.MethodsWe used a well-described mouse model of divergent litter sizes to study the effects of postnatal overfeeding on the central and peripheral ghrelin systems during postnatal development.ResultsMice raised in small litters became overweight during lactation and remained overweight with increased adiposity as adults. Neonatally overnourished mice showed attenuated levels of total and acyl ghrelin in serum and decreased levels of Ghrelin mRNA expression in the stomach during the third week of postnatal life. Normalization of hypoghrelinemia in overnourished pups was relatively ineffective at ameliorating metabolic outcomes, suggesting that small litter pups may present ghrelin resistance. Consistent with this idea, neonatally overnourished pups displayed an impaired central response to peripheral ghrelin. The mechanisms underlying this ghrelin resistance appear to include diminished ghrelin transport into the hypothalamus.ConclusionsEarly postnatal overnutrition results in central resistance to peripheral ghrelin during important periods of hypothalamic development. Because ghrelin signaling has recently been implicated in the neonatal programming of metabolism, these alterations in the ghrelin system may contribute to the metabolic defects observed in postnatally overnourished mice.

Litter size reduction alters insulin signaling in the ventral tegmental area and influences dopamine-related behaviors in adult rats

Postnatal overfeeding is a well-known model of early-life induced obesity and glucose intolerance in rats. However, little is known about its impact on insulin signaling in specific brain regions such as the mesocorticolimbic system, and its putative effects on dopamine-related hedonic food intake in adulthood. For this study, rat litters were standardized to 4 (small litter – SL) or 8 pups (control – NL) at postnatal day 1. Weaning was at day 21, and all tests were conducted after day 60 of life in male rats. In Experiment 1, we demonstrated that the SL animals were heavier than the NL at all time points and had decreased AKT/pAKT ratio in the Ventral Tegmental Area (VTA), without differences in the skeletal muscle insulin signaling in response to insulin injection. In Experiment 2, the standard rat chow intake was addressed using an automated system (BioDAQ, Research Diets®), and showed no differences between the groups. On the other hand, the SL animals ingested more sweet food in response to the 1min tail-pinch challenge and did not develop conditioned place preference to sweet food. In Experiment 3 we showed that the SL rats had increased VTA TH content but had no difference in this protein in response to a sweet food challenge, as the NL had. The SL rats also showed decreased levels of dopamine D2 receptors in the nucleus accumbens. Here we showed that early postnatal overfeeding was linked to an altered functioning of the mesolimbic dopamine pathway, which was associated with altered insulin signaling in the VTA, suggesting increased sensitivity, and expression of important proteins of the dopaminergic system.

Demography of the giant otter (Pteronura brasiliensis) in Manu National Park, south-eastern Peru: implications for conservation.

The giant otter (Pteronura brasiliensis) is an endangered semi-aquatic carnivore of South America. We present findings on the demography of a population inhabiting the floodplain of Manu National Park, south-eastern Peru, arising from 14 annual dry season censuses over a 16 year period. The breeding system of territorial groups, including only a single breeding female with non-reproductive adult ‘helpers’, resulted in a low intrinsic rate of increase (0.03) and a slow recovery from decades of hunting for the pelt trade. This is explained by a combination of factors: (1) physiological traits such as late age at first reproduction and long generation time, (2) a high degree of reproductive skew, (3) small litters produced only once a year, and (4) a 50% mortality between den emergence and age of dispersal, as well as high mortality amongst dispersers (especially males). Female and male giant otters show similar traits with respect to average reproductive life-spans (female 5.4 yrs., male 5.2 yrs.) and average cub productivity (female 6.9, male 6.7 cubs per lifetime); the longest reproductive life spans were 11 and 13 years respectively. Individual reproductive success varied substantially and depended mainly on the duration of dominance tenure in the territory. When breeding females died, the reproductive position in the group was usually occupied by sisters or daughters (n = 11), with immigrant male partners. Male philopatry was not observed. The vulnerability of the Manu giant otter population to anthropogenic disturbance emphasises the importance of effective protection of core lake habitats in particular. Riverine forests are the most endangered ecosystem in the Department of Madre de Dios due to the concentration of gold mining, logging and agricultural activities in floodplains, highlighting the need for a giant otter habitat conservation corridor along the Madre de Dios River.

58. Impact of neonatal nutrition on long-term programming of neuroimmune function

Central inflammation, particularly in feeding-regulatory hypothalamic circuitry, is strongly associated with obesity. Increased hypothalamic inflammation leads to leptin and insulin resistance, disrupting satiety signalling and encouraging food intake. While this dietary-induced dysregulation of metabolic signalling can occur at any stage of life, the early developmental period is known to be particularly sensitive to changes in the nutritional environment. We have previously shown that rats raised in small litters of 4 (SL) receive greater access to their dam’s milk and exhibit an overweight phenotype throughout life, compared to control litters of 12 (CL). These SL rats also demonstrate increased neuroinflammatory responses to an immune challenge with lipopolysaccharide (LPS) in adulthood. Our aim was to determine whether this exacerbated pro-inflammatory phenotype may be mediated by developmental programming of microglial function. We thus examined inflammatory profiles, including microglial density and morphology, in rats raised in SL or CL during neonatal, juvenile and adult life. Our data indicate that neonatal overfeeding leads to increased numbers of Iba-1 positive microglial cells in the paraventricular nucleus of the hypothalamus that persist into adulthood. Moreover, this increased Iba-1 immunolabeling is associated with increased interleukin-6 (IL-6) and Toll-like receptor 4 (TLR4) hypothalamic and hippocampal gene expression. These findings suggest neonatal overfeeding can alter microglial maturation inducing long-term programming of neuroimmune function, and contributing to the continual disruption of feeding and metabolic pathways.