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Developmental plasticity allows organisms to increase the fit between their phenotype and their early-life environment. The extent to which such plasticity also enhances adult fitness is not well understood, however, particularly when early-life and adult environments differ substantially. Using a cross-factorial design that manipulated diet at two life stages, we examined predictions of major hypotheses—silver spoon, environmental matching, and thrifty phenotype—concerning the joint impacts of early-life and adult diets on adult morphology/display traits, survival, and reproductive allocation. Overall, results aligned with the silver spoon hypothesis, which makes several predictions based on the premise that development in poor-quality environments constrains adult performance. Males reared and bred on a low-protein diet had lower adult survivorship than other male treatment groups; females' survivorship was higher than males' and not impacted by early diet. Measures of allocation to reproduction primarily reflected breeding diet, but where natal diet impacted reproduction, results supported the silver spoon. Both sexes showed reduced expression of display traits when reared on a low-protein diet. Results accord with other studies in supporting the relevance of the silver spoon hypothesis to birds and point to significant ramifications of sex differences in early-life viability selection on the applicability/strength of silver spoon effects. [ABSTRACT FROM AUTHOR]

The observational findings of Barker’s original epidemiological studies were generalized as the Barker hypothesis and extended as the Developmental Origins of Health and Disease (DOHaD) theory. Barker et al. proposed that low birthweight (LBW) was associated with the occurrence of various noncommunicable diseases (NCDs) later in life. In other words, LBW itself is associated with the development of NCDs. This led to the DOHaD theory which proposed that an organism may have a specific period of developmental plasticity that is highly sensitive to the factors in its environment, and that combinations of acquired constitution and environmental factors may adversely affect health and risk the formation of NCDs. Due to undernutrition during the fetal period, the fetus acquires an energy-saving constitution called a thrifty phenotype due to adaptations of the metabolic and endocrine systems. It has been suggested that stimuli experienced early in development can persist throughout life and induce permanent physiological changes that predispose to NCDs. It has since become clear that the adverse environmental effects during the prenatal period are also intergenerationally and transgenerationally inherited, affecting the next generation. It has been shown that nutritional interventions such as methyl-donner and epigenome editing can restore some of the impaired functions and reduce the risk of developing some diseases in the next generation. This review thus outlines the mechanisms underlying various disease risk formations and their genetic programs for the next generation, which are being elucidated through studies based on our fetal undernutrition rat models.

Resumen: La obesidad es un problema grave que representa una alta carga para la salud de las personas y sus familias: genera una mayor discapacidad, pérdida de productividad, aumento de enfermedades y muerte prematura. Tradicionalmente, se ha considerado que la patogénesis de la obesidad es el resultado de un desbalance entre la ingesta y el gasto de energía que favorece el aumento de peso. Sin embargo, corresponde a una interacción más compleja entre factores genéticos, ambientales y conductuales.Varios estudios se han centrado en los principios de la termodinámica aplicados a los sensores de energía del cuerpo humano, como activadores de la respuesta metabólica frente a períodos de ayuno y sobrealimentación, para determinar fenotipos metabólicos o individuos que son más susceptibles a variaciones en el peso corporal. La identificación de fenotipos metabólicos permitiría establecer estrategias preventivas o terapias personalizadas para controlar el exceso de peso, favorecer la recuperación de un peso saludable y evitar o controlar los problemas de salud asociados.El objetivo de esta revisión es analizar las características del fenotipo metabólico ahorrador, y los mecanismos fisiológicos involucrados, que permitan proyectar futuras estrategias individualizadas para la prevención y/o tratamiento de pacientes con sobrepeso u obesidad. Summary: Obesity is a serious problem that represents a sizeable burden on the health of individuals and their families: it generates greater disability, reduces productivity, increases disease and premature death. Traditionally, the pathogenesis of obesity has been thought to be the result of an imbalance between energy intake and expenditure that favors weight gain. However, it corresponds to a more complex interaction between genetic, environmental, and behavioral factors.Several studies have focused on thermodynamic principles applied to energy sensors in humans that trigger different metabolic responses when exposed to periods of both fasting and overfeeding. Such studies help determine the metabolic phenotypes of individuals who are more susceptible to variations in body weight. The identification of metabolic phenotypes may aid in the development of preventive strategies, such as personalized therapies to control excess weight, favor the recovery of a healthy weight and avoid or control associated health problems.The aim of this review is to analyze the characteristics of the thrifty metabolic phenotype, and the physiological mechanisms involved, that will allow the design of future individualized strategies for the prevention and/or treatment of patients with overweight or obesity.

Early-life malnutrition increases adult disease risk in humans, but the causal changes in gene regulation, signaling, and metabolism are unclear. In the roundworm Caenorhabditis elegans, early-life starvation causes well-fed larvae to develop germline tumors and other gonad abnormalities as adults. Furthermore, reduced insulin/IGF signaling during larval development suppresses these starvationinduced abnormalities. How early-life starvation and insulin/IGF signaling affect adult pathology is unknown. We show that early-life starvation has pervasive effects on adult gene expression which are largely reversed by reduced insulin/IGF signaling following recovery from starvation. Early-life starvation increases adult fatty-acid synthetase fasn-1 expression in daf-2 insulin/IGF signaling receptor-dependent fashion, and fasn-1/FASN promotes starvation-induced abnormalities. Lipidomic analysis reveals increased levels of phosphatidylcholine in adults subjected to early-life starvation, and supplementation with unsaturated phosphatidylcholine during development suppresses starvation-induced abnormalities. Genetic analysis of fatty-acid desaturases reveals positive and negative effects of desaturation on development of starvation-induced abnormalities. In particular, the ω3 fatty-acid desaturase fat-1 and the Δ5 fatty-acid desaturase fat-4 inhibit and promote development of abnormalities, respectively. fat-4 is epistatic to fat-1, suggesting that arachidonic acid-containing lipids promote development of starvation-induced abnormalities, and supplementation with ARA enhanced development of abnormalities. This work shows that early-life starvation and insulin/IGF signaling converge on regulation of adult lipid metabolism, affecting stem-cell proliferation and tumor formation. [ABSTRACT FROM AUTHOR]

Context: A greater decrease in 24-hour energy expenditure (24hEE) during short-term fasting is indicative of a thrifty phenotype. Objective: As ghrelin and the growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis are implicated in the regulation of energy intake and metabolism, we investigated whether ghrelin, GH, and IGF-1 concentrations mediate the fasting-induced decrease in 24hEE that characterizes thriftiness. Methods: In 47 healthy individuals, 24hEE was measured in a whole-room indirect calorimeter both during 24-hour eucaloric and fasting conditions. Plasma total ghrelin, GH, and IGF-1 concentrations were measured by enzyme-linked immunosorbent assay after an overnight fast the morning before and after each 24-hour session. Results: During 24-hour fasting, on average 24hEE decreased by 8.0% (P < .001), GH increased by ~5-fold (P < .001), whereas ghrelin (mean +23 pg/mL) and IGF-1 were unchanged (both P ≥ .19) despite a large interindividual variability in ghrelin change (SD 150 pg/mL). Greater fasting-induced increase in ghrelin was associated with a greater decrease in 24hEE during 24-hour fasting (r = –0.42, P = .003), such that individuals who increased ghrelin by 200 pg/mL showed an average decrease in 24hEE by 55 kcal/day. Conclusion: Short-term fasting induced selective changes in the ghrelin/GH/IGF-1 axis, specifically a ghrelin-independent GH hypersecretion that did not translate into increased IGF-1 concentrations. Greater increase in ghrelin after 24-hour fasting was associated with greater decrease in 24hEE, indicating ghrelin as a novel biomarker of increased energy efficiency of the thrifty phenotype. [ABSTRACT FROM AUTHOR]

Aims: It is well established that low birthweight is associated with subsequent risk of type 2 diabetes (T2DM). The aim of our study was to use a large birth cohort linked to a national diabetes registry to investigate how birthweight impacts the phenotype at diagnosis of T2DM and the subsequent rate of glycaemic deterioration. Methods: We linked the Walker Birth Cohort (48,000 births, 1952–1966, Tayside, Scotland) to the national diabetes registry in Scotland (SCI‐Diabetes). Birthweight was adjusted for gestational age. Simple linear regression was performed to assess the impact of the adjusted birthweight on the diabetes phenotype at diagnosis. This was then built up into a multiple regression model to allow for the adjustment of confounding variables. A cox proportional hazards model was then used to evaluate the impact of birthweight on diabetes progression. Results: Lower birthweights were associated with a 293 day younger age of diagnosis of T2DM per 1 kg reduction in birthweight, p = 0.005; and a 1.29 kg/m2 lower BMI at diagnosis per 1 kg reduction in birthweight, p < 0.001. There was no significant association of birthweight on diabetes progression. Conclusion: For the first time, we have shown that a lower birthweight is associated with younger onset of T2DM, with those with lower birthweight also being slimmer at diagnosis. These results suggest that lower birthweight impacts on T2DM phenotype via reduced beta‐cell function rather than insulin resistance. [ABSTRACT FROM AUTHOR]

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Early life conditions can have lifelong impacts on survival and fitness. Silver spoon effects occur when favorable early life conditions provide advantages through adulthood, even if conditions worsen. Alternatively, compensatory growth allows organisms initially reared in unfavorable conditions to grow more quickly than expected should conditions improve. We examined these possibilities in the American Toad, Anaxyrus americanus, by rearing larvae in low and high competition environments and then transferring them to either high- or low-resource levels. We measured growth one-week post-transfer and toadlet size after metamorphosis. We also dissected larvae and toadlets from each treatment to examine effects on organ size. Before transfer, larvae reared with low competition grew significantly faster than those reared with high competition. Consistent with the silver spoon hypothesis, these larvae ate significantly more food, continued to grow faster post-transfer, and metamorphosed into larger toadlets with smaller livers and larger guts than those initially reared with high competition, despite having the same food availability within a resource level. Overall, our study demonstrates that larvae initially reared in favorable conditions maintain a growth advantage through metamorphosis even if resource levels decline. Future studies should explore the effects of this advantage post-metamorphosis and into adulthood. [ABSTRACT FROM AUTHOR]

Nutritional variation across the lifetime can have significant and sex-specific impacts on fitness. Using Drosophila melanogaster, we measured these impacts by testing the effects on life span and reproductive success of high or low yeast content in developmental versus adult diets, separately for each sex. We tested two hypotheses: that dietary mismatches between development and adulthood are costly and that any such costs are sex-specific. Overall, the results revealed the rich and complex responses of each sex to dietary variation across the lifetime. Contrary to the first hypothesis, dietary mismatches between developmental and adult life stages were not universally costly. Where costs of nutritional variation across the life course did occur, they were sex-, context-, and trait-specific, consistent with hypothesis 2. We found effects of mismatches between developmental and adult diets on reproductive success in females but not males. Adult diet was the main determinant of survival, and life span was significantly longer on high yeast adult food, in comparison to low, in both sexes. Developing on a high yeast diet also benefited adult female life span and reproductive success, regardless of adult diet. In contrast, a high yeast developmental diet was only beneficial for male life span when it was followed by low yeast adult food. Adult diet affected mating frequency in opposing directions, with males having higher mating frequency on high and females on low, with no interaction with developmental diet for either sex. The results emphasize the importance of sex differences and of the directionality of dietary mismatches in the responses to nutritional variation. [ABSTRACT FROM AUTHOR]

In this article, we explore the potential of Warin et al.'s concept of biohabitus (a set of embodied biological and social dispositions) as a conceptual tool for the understanding of mechanisms behind the "obesity epidemic." Elaborating on this concept, we argue that a context of food scarcity gives rise to a biohabitus geared to energy‐saving, expressed in both biological (the thrifty genotype/phenotype hypotheses) and symbolic dispositions (Bourdieu's "taste of necessity"), and the interaction between this type of biohabitus and changes in the food‐related environment results in increased body mass index. We exemplify the use of this framework by applying it to the case of Mexico, a middle‐income Latin American country with one of the highest prevalences of obesity worldwide. The example shows how the concept of biohabitus can help researchers move beyond disciplinary explanations, towards a more complex understanding of the conjunction of social and biological processes that result in differential patterns of health and disease. [ABSTRACT FROM AUTHOR]

Background A metabolic adaptation, defined as an increase in energy expenditure (EE) beyond what is expected with weight gain during overfeeding (OF), has been reported but also refuted. Much of the inconsistency stems from the difficulty in conducting large, well-controlled OF studies in humans. Objectives The primary aim of this study was to determine whether a metabolic adaptation to OF exists and if so, attenuates weight gain. Methods Thirty-five young adults consumed 40% above their baseline energy requirements for 8 wk, and sleeping metabolic rate (SMR) and 24-h sedentary energy expenditure (24h-EE) were measured before and after OF. Subjects were asked to return for a 6-mo post-OF follow-up visit to measure body weight, body composition, and physical activity. Results After adjusting for gains in fat-free mass and fat mass, SMR increased by 43 ± 123 kcal/d more than expected (P  = 0.05) and 24h-EE by 23 ± 139 kcal/d (P  = 0.34), indicating an overall lack of metabolic adaptation during OF despite a wide variability in the response. Among the 30 subjects who returned for the 6-mo follow-up visit, those who had a lower-than-predicted SMR (basal EE) retained more of the fat gained during OF. Likewise, subjects displaying a higher-than-predicted sedentary 24h-EE lost significantly more fat during the 6-mo follow-up. Conclusions Metabolic adaptation to OF was on average very small but variable between subjects, revealing "thrifty" or "spendthrift" metabolic phenotypes related to body weight loss 6 mo later. This trial was registered at clinicaltrials.gov as NCT01672632. [ABSTRACT FROM AUTHOR]

Background: Litter size affects fetal development but its relation to diet-induced fatty liver later in life is unknown.Objectives: This aim of this study was to test the hypothesis that litter size influences postweaning fatty liver development in response to soybean oil-supplemented diet.Methods: Weanling twin (TW) or triplet (TP) male lambs (n = 16) were fed a control diet or 2% soybean oil-supplemented diet (SO) for 90 d. Liver tissue morphology, biochemical parameters, and lipid metabolic enzymes were determined. Hepatic gene expression was analyzed by RNA sequencing (n = 3), followed by enrichment analysis according to Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes. Differentially expressed genes involved in lipid metabolism were further verified by quantitative reverse transcriptase-polymerase chain reaction (n = 4). All data were analyzed by a 2-factor ANOVA, apart from differentially expressed genes, which were identified by the Benjamini-Hochberg approach (q value ≤0.05).Results: SO increased liver triglyceride (by 55%) and nonesterified fatty acid (by 54%) concentrations in TPs (P ≤ 0.05) but not in TWs (P > 0.05). SO also induced a 2.3- and 2.1-fold increase in the liver steatosis score of TPs and TWs, respectively (P ≤ 0.05). Moreover, SO reduced the activity of lipolytic enzymes including hepatic lipase and total lipase in TPs by 47% and 25%, respectively (P ≤ 0.05). In contrast, activities of lipogenic enzymes, including malic enzyme and acetyl coenzyme A carboxylase, were significantly higher in TPs (P ≤ 0.05). Moreover, TPs had higher expression of lipogenic genes, such as FASN (by 45%) and APOB (by 72%), and lower expression of lipolytic genes, such as PRKAA2 (by 28%) and CPT1A (by 43%), compared with TWs (P ≤ 0.05).Conclusions: TPs have a gene expression profile that is more susceptible to SO-induced fatty liver than that of TWs, which indicates that insufficient maternal nutrient supply at fetal and neonatal stages may increase the risk of nonalcoholic fatty liver disease. [ABSTRACT FROM AUTHOR]

The concept of developmental origins of diseases has gained a huge interest in recent years and is a constantly emerging scientific field. First observations hereof originated from epidemiological studies, linking impaired birth outcomes to adult chronic, noncommunicable disease. By now there is a considerable amount of both epidemiological and experimental evidence highlighting the impact of early life events on later life disease susceptibility. Albeit far from being completely understood, more recent studies managed to elucidate underlying mechanisms, with epigenetics having become almost synonymous with developmental programming. The aim of this review was to give a comprehensive overview of various aspects and mechanisms of developmental origins of diseases. Starting from initial research foci mainly centered on a nutritionally impaired intrauterine environment, more recent findings such as postnatal nutrition, preterm birth, paternal programming and putative interventional approaches are summarized. The review outlines general underlying mechanisms and particularly discusses mechanistic explanations for sexual dimorphism in developmental programming. Furthermore, novel hypotheses are presented emphasizing a non-mendelian impact of parental genes on the offspring's phenotype.

ABSTRACT: Developmental plasticity, a phenomenon of importance in both evolutionary biology and human studies of the developmental origins of health and disease (DOHaD), enables organisms to respond to their environment based on previous experience without changes to the underlying nucleotide sequence. Although such phenotypic responses should theoretically improve an organism's fitness and performance in its future environment, this is not always the case. Herein, we first discuss epigenetics as an adaptive mechanism of developmental plasticity and use signaling theory to provide an evolutionary context for DOHaD phenomena within a generation. Next, we utilize signalling theory to identify determinants of adaptive developmental plasticity, detect sources of random variability – also known as process errors that affect maintenance of an epigenetic signal (DNA methylation) over time, and discuss implications of these errors for an organism's health and fitness. Finally, we apply life‐course epidemiology conceptual models to inform study design and analytical strategies that are capable of parsing out the potential effects of process errors in the relationships among an organism's early environment, DNA methylation, and phenotype in a future environment. Ultimately, we hope to foster cross‐talk and interdisciplinary collaboration between evolutionary biology and DOHaD epidemiology, which have historically remained separate despite a shared interest in developmental plasticity. [ABSTRACT FROM AUTHOR]

Evidence suggests that both high and low birth weight children have increased the risk for obesity and the metabolic syndrome in adulthood. Previously we have found altered feeding behaviour and food preferences in pre-school children and adults born with low birth weight. In this study, we investigated if birth weight was associated with different intake of fat, carbohydrate and/or protein at 6–12 years of age. This is a cross-sectional study where 255 guardians answered online and telephone questions including anthropometrics and demographic data, parental family food rules (food control, encouragement and restriction) and a complete web-based FFQ for their children (130 boys and 125 girls). Baseline demographic and parental food rules characteristics did not differ accordingly to sex. Linear regression models were conducted separately for each sex, adjusted for income, age and maternal age. There were no differences in total energy intake, but energy density (ED, energy content/g) was negatively associated with birth weight in boys. Macronutrient analysis showed that ED intake was from a greater intake of fat. Birth weight was not a significant predictor of protein and carbohydrate intake in boys. In girls, we saw a positive correlation between fat intake and cholesterol intake v. birth weight, but no association with ED intake (results did not remain after adjustment). The study shows that low birth weight is associated with altered fat intake in childhood in a sex-specific manner. It is likely that biological factors such as fetal programming of homoeostatic and/or hedonic pathways influencing food preferences are involved in this process. [ABSTRACT FROM AUTHOR]

Early-life conditions can drive ageing patterns and life history strategies throughout the lifespan. Certain social, genetic and nutritional developmental conditions are more likely to produce high-quality offspring: those with good likelihood of recruitment and productivity. Here, we call such conditions 'favoured states' and explore their relationship with physiological variables during development in a long-lived seabird, the black-legged kittiwake ( Rissa tridactyla). Two favoured states were experimentally generated by manipulation of food availability and brood size, while hatching order and sex were also explored as naturally generating favoured states. Thus, the favoured states we explored were high food availability, lower levels of sibling competition, hatching first and male sex. We tested the effects of favoured developmental conditions on growth, stress, telomere length (a molecular marker associated with lifespan) and nestling survival. Generation of favoured states through manipulation of both the nutritional and social environments furthered our understanding of their relative contributions to development and phenotype: increased food availability led to larger body size, reduced stress and higher antioxidant status, while lower sibling competition (social environment) led to lower telomere loss and longer telomere lengths in fledglings. Telomere length predicted nestling survival, and wing growth was also positively correlated with telomere length, supporting the idea that telomeres may indicate individual quality, mediated by favoured states. [ABSTRACT FROM AUTHOR]

Developmental plasticity is a key feature of many organisms and individuals can benefit from early programming to optimize their phenotypes for the expected environmental conditions. However, environmental conditions may sometimes change unexpectedly. Mismatches between early and adult life, for example, can have important repercussions for adult phenotypes, potentially leading to better performance under matched than mismatched conditions as predicted by the predictive adaptive response hypothesis. We conducted a long-term experimental manipulation of dietary conditions in a population of zebra finches, Taeniopygia guttata . Broods were exposed to two early nutritional treatments until independence and we used a split-brood design to independently manipulate nutritional conditions after independence to create matched and mismatched nutritional environments in later life. Developmental trajectories of all individuals were followed for more than 5 years and we scored behavioural responses in trials in a special environment and while interacting with a special object three times during adult life. Overall, we found no evidence for early programming affecting morphology. Tarsus and wing length were exclusively influenced by the early nutrition. Body weight showed lasting effects of the early treatment and independent effects of nutritional condition during adulthood, but no effects of environmental matching or mismatching. Special-object trials showed effects of the adult nutritional treatment while environmental matching affected hopping activity in special environments. These behavioural responses showed substantial long-term individual stability over a 3-month period and were only marginally smaller when measured over a period of more than 4 years. Interestingly, survival of individuals from low-quality early nutritional condition was higher compared with high-quality early condition individuals, which became evident only after years of survival monitoring. Beyond the nutritional treatment itself, we found sizable brood identity effects that slowly but steadily declined with age, indicating a significant but decaying effect of natural variation in parental provisioning on adult phenotypes. [ABSTRACT FROM AUTHOR]

The concept of the thrifty phenotype, first proposed by Hales and Barker, is now widely used in medical research, often in contrast to the thrifty genotype model, to interpret associations between early-life experience and adult health status. Several evolutionary models of the thrifty phenotype, which refers to developmental plasticity, have been presented. These include (A) the weather forecast model of Bateson, (B) the maternal fi tness model of Wells, (C) the intergenerational phenotypic inertia model of Kuzawa, and (D) the predictive adaptive response model of Gluckman and Hanson. These models are compared and contrasted, in order to assess their relative utility for understanding human ontogenetic development. The most broadly applicable model is model A, which proposes that developing organisms respond to cues of environmental quality, and that mismatches between this forecast and subsequent reality generate significant adverse effects in adult phenotype. The remaining models all address in greater detail what kind of information is provided by such a forecast. Whereas both models B and C emphasise the adaptive benefits of exploiting information about the past, encapsulated in maternal phenotype, model D assumes that the fetus uses cues about the present external environment to predict its probable adult environment. I argue that for humans, with a disproportionately long period between the closing of sensitive windows of plasticity and the attainment of reproductive maturity, backward-looking models B and C represent a better approach, and indicate that the developing offspring aligns itself with stable cues of maternal phenotype so as to match its energy demand with maternal capacity to supply. In contrast, the predictive adaptive response model D over-estimates the capacity of the offspring to predict the future, and also fails to address the long-term parent-offspring dynamics of human development. Differences between models have implications for the design of public health interventions.

The concept of developmental origins of diseases has gained a huge interest in recent years and is a constantly emerging scientific field. First observations hereof originated from epidemiological studies, linking impaired birth outcomes to adult chronic, noncommunicable disease. By now there is a considerable amount of both epidemiological and experimental evidence highlighting the impact of early life events on later life disease susceptibility. Albeit far from being completely understood, more recent studies managed to elucidate underlying mechanisms, with epigenetics having become almost synonymous with developmental programming. The aim of this review was to give a comprehensive overview of various aspects and mechanisms of developmental origins of diseases. Starting from initial research foci mainly centered on a nutritionally impaired intrauterine environment, more recent findings such as postnatal nutrition, preterm birth, paternal programming and putative interventional approaches are summarized. The review outlines general underlying mechanisms and particularly discusses mechanistic explanations for sexual dimorphism in developmental programming. Furthermore, novel hypotheses are presented emphasizing a non-mendelian impact of parental genes on the offspring's phenotype. [ABSTRACT FROM AUTHOR]

Objectives: Substantial weight loss through intense dietary regimens is thought to ameliorate endothelial dysfunction in obesity. It is less clear whether similar improvements can be achieved with modest dietary interventions. This study aimed to identify the parameters of endothelial cell status in obesity that are affected by mild calorie restriction. Methods: Human umbilical vein endothelial cells (EA.hy926 line) in culture were exposed pairwise to serum from 57 individuals with simple obesity (BMI > 30 kg/m) collected before and after 8-week dietary intervention with energy deficit of 300-500 kcal/day. Results: Analysis of endothelial transcriptome suggested that the intervention could impact on endothelial cell growth. Cell proliferation was measured with the MTT test and verified by [H]-thymidine incorporation. The participants were categorized according to a change in proliferation over time. Significant decrease in endothelial cell proliferation correlated with the extent of weight loss in men, but not in women. This effect corresponded with changes in serum levels of leptin and adiponectin, but was not related to serum concentrations of several known angiogenic mediators (VEGF, MCP-1, TSP-1, MMP-9, angiopoietin-2). Conclusion: Direction and magnitude of changes in serum-induced endothelial cell proliferation identifies patients with the greatest weight loss in response to modest calorie restriction. [ABSTRACT FROM AUTHOR]

Life-history theory predicts that exposure to conditions typical of low socioeconomic status (SES) during childhood will calibrate development in ways that promote survival in harsh and unpredictable ecologies. Guided by this insight, the current research tested the hypothesis that low childhood SES will predict eating in the absence of energy need. Across three studies, we measured (Study 1) or manipulated (Studies 2 and 3) participants' energy need and gave them the opportunity to eat provided snacks. Participants also reported their SES during childhood and their current SES. Results revealed that people who grew up in high-SES environments regulated their food intake on the basis of their immediate energy need; they ate more when their need was high than when their need was low. This relationship was not observed among people who grew up in low-SES environments. These individuals consumed comparably high amounts of food when their current energy need was high and when it was low. Childhood SES may have a lasting impact on food regulation. [ABSTRACT FROM AUTHOR]

• The thrifty phenotype hypothesis predicts development of obesity and early puberty. • There is also relatively strong support for the fetal overnutrition hypothesis. • These alterative hypotheses are typically examined in isolation. • We propose an integrated model of both hypotheses for obesity and early puberty. • Under-studied sex and race/ethnicity differences may modify aspects of this model. We outline an operationalization and extension of the thrifty phenotype and fetal overnutrition hypotheses, two developmental hypotheses stemming from the developmental origins of health and disease (DOHaD) perspective, for developmental pathways from preconception and prenatal risk through child growth to early puberty. The available evidence suggests that both the thrifty phenotype and fetal overnutrition pathways have direct and indirect effects on child growth and pubertal timing, with potential moderating effects of sex and race. Further investigating the hypothesized pathways will be helpful toward identifying youth who are at high risk of earlier pubertal timing, who may be on trajectories leading to poor health in adolescence and adulthood. Future studies should investigate the role of the pathways in predicting mental and physical health outcomes which may lead to a better understanding of health trajectories across the life course. [ABSTRACT FROM AUTHOR]

To explore the logic of evolutionary explanations of obesity we modelled food consumption in an animal that minimizes mortality (starvation plus predation) by switching between activities that differ in energy gain and pre-dation. We show that if switching does not incur extra predation risk, the animal should have a single threshold level of reserves above which it performs the safe activity and below which it performs the dangerous activity. The value of the threshold is determined by the environmental conditions, implying that animals should have variable 'set points'. Selection pressure to prevent energy stores exceeding the optimal level is usually weak, suggesting that immediate rewards might easily overcome the controls against becoming overweight. The risk of starvation can have a strong influence on the strategy even when starvation is extremely uncommon, so the incidence of mortality during famine in human history may be unimportant for explanations for obesity. If there is an extra risk of switching between activities, the animal should have two distinct thresholds: one to initiate weight gain and one to initiate weight loss. Contrary to the dual intervention point model, these thresholds will be inter-dependent, such that altering the predation risk alters the location of both thresholds; a result that undermines the evolutionary basis of the drifty genes hypothesis. Our work implies that understanding the causes of obesity can benefit from a better understanding of how evolution shapes the mechanisms that control body weight. [ABSTRACT FROM AUTHOR]

Both developmental nutrition and adult nutrition affect life-history traits; however, little is known about whether the effect of developmental nutrition depends on the adult environment experienced. We used the fruit fly to determine whether life-history traits, particularly life span and fecundity, are affected by developmental nutrition, and whether this depends on the extent to which the adult environment allows females to realize their full reproductive potential. We raised flies on three different developmental food levels containing increasing amounts of yeast and sugar: poor, control, and rich. We found that development on poor or rich larval food resulted in several life-history phenotypes indicative of suboptimal conditions, including increased developmental time, and, for poor food, decreased adult weight. However, development on poor larval food actually increased adult virgin life span. In addition, we manipulated the reproductive potential of the adult environment by adding yeast or yeast and a male. This manipulation interacted with larval food to determine adult fecundity. Specifically, under two adult conditions, flies raised on poor larval food had higher reproduction at certain ages - when singly mated this occurred early in life and when continuously mated with yeast this occurred during midlife. We show that poor larval food is not necessarily detrimental to key adult life-history traits, but does exert an adult environment-dependent effect, especially by affecting virgin life span and altering adult patterns of reproductive investment. Our findings are relevant because (1) they may explain differences between published studies on nutritional effects on life-history traits; (2) they indicate that optimal nutritional conditions are likely to be different for larvae and adults, potentially reflecting evolutionary history; and (3) they urge for the incorporation of developmental nutritional conditions into the central life-history concept of resource acquisition and allocation. [ABSTRACT FROM AUTHOR]