Adult-Onset Obesity Reveals Prenatal Programming of Glucose-Insulin Sensitivity in Male Sheep Nutrient Restricted during Late Gestation

BACKGROUND: Obesity invokes a range of metabolic disturbances, but the transition from a poor to excessive nutritional environment may exacerbate adult metabolic dysfunction. The current study investigated global maternal nutrient restriction during early or late gestation on glucose tolerance and insulin sensitivity in the adult offspring when lean and obese. METHODS/PRINCIPAL FINDINGS: Pregnant sheep received adequate (1.0M; CE, n = 6) or energy restricted (0.7M) diet during early (1-65 days; LEE, n = 6) or late (65-128 days; LEL, n = 7) gestation (term approximately 147 days). Subsequent offspring remained on pasture until 1.5 years when all received glucose and insulin tolerance tests (GTT & ITT) and body composition determination by dual energy x-ray absorptiometry (DXA). All animals were then exposed to an obesogenic environment for 6-7 months and all protocols repeated. Prenatal dietary treatment had no effect on birth weight or on metabolic endpoints when animals were 'lean' (1.5 years). Obesity revealed generalised metabolic 'inflexibility' and insulin resistance; characterised by blunted excursions of plasma NEFA and increased insulin(AUC) (from 133 to 341 [s.e.d. 26] ng.ml(-1).120 mins) during a GTT, respectively. For LEL vs. CE, the peak in plasma insulin when obese was greater (7.8 vs. 4.7 [s.e.d. 1.1] ng.ml(-1)) and was exacerbated by offspring sex (i.e. 9.8 vs. 4.4 [s.e.d. 1.16] ng.ml(-1); LEL male vs. CE male, respectively). Acquisition of obesity also significantly influenced the plasma lipid and protein profile to suggest, overall, greater net lipogenesis and reduced protein metabolism. CONCLUSIONS: This study indicates generalised metabolic dysfunction with adult-onset obesity which also exacerbates and 'reveals' programming of glucose-insulin sensitivity in male offspring prenatally exposed to maternal undernutrition during late gestation. Taken together, the data suggest that metabolic function appears little compromised in young prenatally 'programmed' animals so long as weight is adequately controlled. Nutritional excess in adulthood exacerbates any programmed phenotype, indicating greater vigilance over weight control is required for those individuals exposed to nutritional thrift during gestation

Resolving the Trophic Relations of Cryptic Species: An Example Using Stable Isotope Analysis of Dolphin Teeth

Understanding the foraging ecology and diet of animals can play a crucial role in conservation of a species. This is particularly true where species are cryptic and coexist in environments where observing feeding behaviour directly is difficult. Here we present the first information on the foraging ecology of a recently identified species of dolphin (Southern Australian bottlenose dolphin (SABD)) and comparisons to the common bottlenose dolphin (CBD) in Victoria, Australia, using stable isotope analysis of teeth. Stable isotope signatures differed significantly between SABD and CBD for both δ13C (−14.4‰ vs. −15.5‰ respectively) and δ15N (15.9‰ vs. 15.0‰ respectively), suggesting that the two species forage in different areas and consume different prey. This finding supports genetic and morphological data indicating that SABD are distinct from CBD. In Victoria, the SABD is divided into two distinct populations, one in the large drowned river system of Port Phillip Bay and the other in a series of coastal lakes and lagoons called the Gippsland Lakes. Within the SABD species, population differences were apparent. The Port Phillip Bay population displayed a significantly higher δ15N than the Gippsland Lakes population (17.0‰ vs. 15.5‰), suggesting that the Port Phillip Bay population may feed at a higher trophic level - a result which is supported by analysis of local food chains. Important future work is required to further understand the foraging ecology and diet of this newly described, endemic, and potentially endangered species of dolphin

Reduced Cortisol and Metabolic Responses of Thin Ewes to an Acute Cold Challenge in Mid-Pregnancy: Implications for Animal Physiology and Welfare

Background: Low food availability leading to reductions in Body Condition Score (BCS; 0 indicates emaciation and 5 obesity) in sheep often coincides with low temperatures associated with the onset of winter in New Zealand. The ability to adapt to reductions in environmental temperature may be impaired in animals with low BCS, in particular during pregnancy when metabolic demand is higher. Here we assess whether BCS affects a pregnant animal’s ability to cope with cold challenges. Methods: Eighteen pregnant ewes with a BCS of 2.760.1 were fed to attain low (LBC: BCS2.360.1), medium (MBC: BCS3.260.2) or high BCS (HBC: BCS3.660.2). Shorn ewes were exposed to a 6-h acute cold challenge in a climate-controlled room (wet and windy conditions, 4.460.1uC) in mid-pregnancy. Blood samples were collected during the BCS change phase, acute cold challenge and recovery phase. Results: During the BCS change phase, plasma glucose and leptin concentrations declined while free fatty acids (FFA) increased in LBC compared to MBC (P,0.01, P,0.01 and P,0.05, respectively) and HBC ewes (P,0.05, P,0.01 and P,0.01, respectively). During the cold challenge, plasma cortisol concentrations were lower in LBC than MBC (P,0.05) and HBC ewes (P,0.05), and FFA and insulin concentrations were lower in LBC than HBC ewes (P,0.05 and P,0.001, respectively). Leptin concentrations declined in MBC and HBC ewes while remaining unchanged in LBC ewes (P,0.01). Glucose concentrations and internal body temperature (Tcore) increased in all treatments, although peak Tcore tended to be higher in HBC ewes (P,0.1). During the recovery phase, T4 concentrations were lower in LBC ewes (P,0.05). Conclusion: Even though all ewes were able to increase Tcore and mobilize glucose, low BCS animals had considerably reduced cortisol and metabolic responses to a cold challenge in mid-pregnancy, suggesting that their ability to adapt to cold challenges through some of the expected pathways was reduced

Biodiversity of the Deep-Sea Continental Margin Bordering the Gulf of Maine (NW Atlantic): Relationships among Sub-Regions and to Shelf Systems

Background: In contrast to the well-studied continental shelf region of the Gulf of Maine, fundamental questions regarding the diversity, distribution, and abundance of species living in deep-sea habitats along the adjacent continental margin remain unanswered. Lack of such knowledge precludes a greater understanding of the Gulf of Maine ecosystem and limits development of alternatives for conservation and management. Methodology/Principal Findings: We use data from the published literature, unpublished studies, museum records and online sources, to: (1) assess the current state of knowledge of species diversity in the deep-sea habitats adjacent to the Gulf of Maine (39–43uN, 63–71uW, 150–3000 m depth); (2) compare patterns of taxonomic diversity and distribution of megafaunal and macrofaunal species among six distinct sub-regions and to the continental shelf; and (3) estimate the amount of unknown diversity in the region. Known diversity for the deep-sea region is 1,671 species; most are narrowly distributed and known to occur within only one sub-region. The number of species varies by sub-region and is directly related to sampling effort occurring within each. Fishes, corals, decapod crustaceans, molluscs, and echinoderms are relatively well known, while most other taxonomic groups are poorly known. Taxonomic diversity decreases with increasing distance from the continental shelf and with changes in benthic topography. Low similarity in faunal composition suggests the deep-sea region harbours faunal communities distinct from those of the continental shelf. Non-parametric estimators of species richness suggest a minimum of 50% of the deep-sea species inventory remains to be discovered. Conclusions/Significance: The current state of knowledge of biodiversity in this deep-sea region is rudimentary. Our ability to answer questions is hampered by a lack of sufficient data for many taxonomic groups, which is constrained by sampling biases, life-history characteristics of target species, and the lack of trained taxonomists

Increased Cardiovascular Reactivity to Acute Stress and Salt-Loading in Adult Male Offspring of Fat Fed Non-Obese Rats

Diet-induced obesity in rat pregnancy has been shown previously to be associated with consistently raised blood pressure in the offspring, attributed to sympathetic over-activation, but the relative contributions to this phenotype of maternal obesity versus raised dietary fat is unknown. Sprague-Dawley female rats were fed either a control (4.3% fat, n = 11) or lard-enriched (23.6% fat, n = 16) chow 10 days prior to mating, throughout pregnancy and lactation. In conscious adult (9-month-old) offspring cardiovascular parameters were measured (radiotelemetry). The short period of fat-feeding did not increase maternal weight versus controls and the baseline blood pressure was similar in offspring of fat fed dams (OF) and controls (OC). However, adult male OF showed heightened cardiovascular reactivity to acute restraint stress (p<0.01; Δ systolic blood pressure (SBP) and Δheart rate (HR)) with a prolonged recovery time compared to male OC. α1/β-adrenergic receptor blockade normalised the response. Also, after dietary salt-loading (8%-NaCl ad libitum for 1 week) male OF demonstrated higher SBP (p<0.05) in the awake phase (night-time) and increased low/high frequency ratio of power spectral density of HR variability versus OC. Baroreflex gain and basal power spectral density components of the heart rate or blood pressure were similar in male OF and OC. Minor abnormalities were evident in female OF. Fat feeding in the absence of maternal obesity in pregnant rats leads to altered sympathetic control of cardiovascular function in adult male offspring, and hypertension in response to stressor stimuli

Genome-Wide Analysis of Glucocorticoid Receptor Binding Regions in Adipocytes Reveal Gene Network Involved in Triglyceride Homeostasis

Glucocorticoids play important roles in the regulation of distinct aspects of adipocyte biology. Excess glucocorticoids in adipocytes are associated with metabolic disorders, including central obesity, insulin resistance and dyslipidemia. To understand the mechanisms underlying the glucocorticoid action in adipocytes, we used chromatin immunoprecipitation sequencing to isolate genome-wide glucocorticoid receptor (GR) binding regions (GBRs) in 3T3-L1 adipocytes. Furthermore, gene expression analyses were used to identify genes that were regulated by glucocorticoids. Overall, 274 glucocorticoid-regulated genes contain or locate nearby GBR. We found that many GBRs were located in or nearby genes involved in triglyceride (TG) synthesis (Scd-1, 2, 3, GPAT3, GPAT4, Agpat2, Lpin1), lipolysis (Lipe, Mgll), lipid transport (Cd36, Lrp-1, Vldlr, Slc27a2) and storage (S3-12). Gene expression analysis showed that except for Scd-3, the other 13 genes were induced in mouse inguinal fat upon 4-day glucocorticoid treatment. Reporter gene assays showed that except Agpat2, the other 12 glucocorticoid-regulated genes contain at least one GBR that can mediate hormone response. In agreement with the fact that glucocorticoids activated genes in both TG biosynthetic and lipolytic pathways, we confirmed that 4-day glucocorticoid treatment increased TG synthesis and lipolysis concomitantly in inguinal fat. Notably, we found that 9 of these 12 genes were induced in transgenic mice that have constant elevated plasma glucocorticoid levels. These results suggested that a similar mechanism was used to regulate TG homeostasis during chronic glucocorticoid treatment. In summary, our studies have identified molecular components in a glucocorticoid-controlled gene network involved in the regulation of TG homeostasis in adipocytes. Understanding the regulation of this gene network should provide important insight for future therapeutic developments for metabolic diseases

Improving pulse crops as a source of protein, starch and micronutrients

Pulse crops have been known for a long time to have beneficial nutritional profiles for human diets but have been neglected in terms of cultivation, consumption and scientific research in many parts of the world. Broad dietary shifts will be required if anthropogenic climate change is to be mitigated in the future, and pulse crops should be an important component of this change by providing an environmentally sustainable source of protein, resistant starch and micronutrients. Further enhancement of the nutritional composition of pulse crops could benefit human health, helping to alleviate micronutrient deficiencies and reduce risk of chronic diseases such as type 2 diabetes. This paper reviews current knowledge regarding the nutritional content of pea (Pisum sativum L.) and faba bean (Vicia faba L.), two major UK pulse crops, and discusses the potential for their genetic improvement

Preconditioning-induced ischemic tolerance: a window into endogenous gearing for cerebroprotection

Ischemic tolerance defines transient resistance to lethal ischemia gained by a prior sublethal noxious stimulus (i.e., preconditioning). This adaptive response is thought to be an evolutionarily conserved defense mechanism, observed in a wide variety of species. Preconditioning confers ischemic tolerance if not in all, in most organ systems, including the heart, kidney, liver, and small intestine. Since the first landmark experimental demonstration of ischemic tolerance in the gerbil brain in early 1990's, basic scientific knowledge on the mechanisms of cerebral ischemic tolerance increased substantially. Various noxious stimuli can precondition the brain, presumably through a common mechanism, genomic reprogramming. Ischemic tolerance occurs in two temporally distinct windows. Early tolerance can be achieved within minutes, but wanes also rapidly, within hours. Delayed tolerance develops in hours and lasts for days. The main mechanism involved in early tolerance is adaptation of membrane receptors, whereas gene activation with subsequent de novo protein synthesis dominates delayed tolerance. Ischemic preconditioning is associated with robust cerebroprotection in animals. In humans, transient ischemic attacks may be the clinical correlate of preconditioning leading to ischemic tolerance. Mimicking the mechanisms of this unique endogenous protection process is therefore a potential strategy for stroke prevention. Perhaps new remedies for stroke are very close, right in our cells

A Net Energy Analysis of the Global Agriculture, Aquaculture, Fishing and Forestry System

The global agriculture, aquaculture, fishing and forestry (AAFF) energy system is subject to three unsustainable trends: (1) the approaching biophysical limits of AAFF; (2) the role of AAFF as a driver of environmental degradation; and (3) the long-term declining energy efficiency of AAFF due to growing dependence on fossil fuels. In response, we conduct a net energy analysis for the period 1971–2017 and review existing studies to investigate the global AAFF energy system and its vulnerability to the three unsustainable trends from an energetic perspective. We estimate the global AAFF system represents 27.9% of societies energy supply in 2017, with food energy representing 20.8% of societies total energy supply. We find that the net energy-return-on-investment (net EROI) of global AAFF increased from 2.87:1 in 1971 to 4.05:1 in 2017. We suggest that rising net EROI values are being fuelled in part by ‘depleting natures accumulated energy stocks’. We also find that the net energy balance of AAFF increased by 130% in this period, with at the same time a decrease in both the proportion of rural residents and also the proportion of the total population working in AAFF—which decreased from 19.8 to 10.3%. However, this comes at the cost of growing fossil fuel dependency which increased from 43.6 to 62.2%. Given the increasing probability of near-term fossil fuel scarcity, the growing impacts of climate change and environmental degradation, and the approaching biophysical limits of global AAFF, ‘Odum’s hoax’ is likely soon to be revealed