Caloric Restriction Alters the Metabolic Response to a Mixed-Meal: Results from a Randomized, Controlled Trial

OBJECTIVES: To determine if caloric restriction (CR) would cause changes in plasma metabolic intermediates in response to a mixed meal, suggestive of changes in the capacity to adapt fuel oxidation to fuel availability or metabolic flexibility, and to determine how any such changes relate to insulin sensitivity (S(I)). METHODS: Forty-six volunteers were randomized to a weight maintenance diet (Control), 25% CR, or 12.5% CR plus 12.5% energy deficit from structured aerobic exercise (CR+EX), or a liquid calorie diet (890 kcal/d until 15% reduction in body weight)for six months. Fasting and postprandial plasma samples were obtained at baseline, three, and six months. A targeted mass spectrometry-based platform was used to measure concentrations of individual free fatty acids (FFA), amino acids (AA), and acylcarnitines (AC). S(I) was measured with an intravenous glucose tolerance test. RESULTS: Over three and six months, there were significantly larger differences in fasting-to-postprandial (FPP) concentrations of medium and long chain AC (byproducts of FA oxidation) in the CR relative to Control and a tendency for the same in CR+EX (CR-3 month P = 0.02; CR-6 month P = 0.002; CR+EX-3 month P = 0.09; CR+EX-6 month P = 0.08). After three months of CR, there was a trend towards a larger difference in FPP FFA concentrations (P = 0.07; CR-3 month P = 0.08). Time-varying differences in FPP concentrations of AC and AA were independently related to time-varying S(I) (P<0.05 for both). CONCLUSIONS: Based on changes in intermediates of FA oxidation following a food challenge, CR imparted improvements in metabolic flexibility that correlated with improvements in S(I). TRIAL REGISTRATION: ClinicalTrials.gov NCT00099151

Relations Among Anhedonia, Reinforcement Learning, and Global Functioning in Help-seeking Youth

Dysfunction in the neural circuits underlying salience signaling is implicated in symptoms of psychosis and may predict conversion to a psychotic disorder in youth at clinical high risk (CHR) for psychosis. Additionally, negative symptom severity, including consummatory and anticipatory aspects of anhedonia, may predict functional outcome in individuals with schizophrenia-spectrum disorders. However, it is unclear whether anhedonia is related to the ability to attribute incentive salience to stimuli (through reinforcement learning [RL]) and whether measures of anhedonia and RL predict functional outcome in a younger, help-seeking population. We administered the Salience Attribution Test (SAT) to 33 participants who met criteria for either CHR or a recent-onset psychotic disorder and 29 help-seeking youth with nonpsychotic disorders. In the SAT, participants must identify relevant and irrelevant stimulus dimensions and be sensitive to different reinforcement probabilities for the 2 levels of the relevant dimension ("adaptive salience"). Adaptive salience attribution was positively related to both consummatory pleasure and functioning in the full sample. Analyses also revealed an indirect effect of adaptive salience on the relation between consummatory pleasure and both role (αβ = .22, 95% CI = 0.02, 0.48) and social functioning (αβ = .14, 95% CI = 0.02, 0.30). These findings suggest a distinct pathway to poor global functioning in help-seeking youth, via impaired reward sensitivity and RL

Evidence of a metabolic memory to early-life dietary restriction in male C57BL/6 mice

&lt;p&gt;Background: Dietary restriction (DR) extends lifespan and induces beneficial metabolic effects in many animals. What is far less clear is whether animals retain a metabolic memory to previous DR exposure, that is, can early-life DR preserve beneficial metabolic effects later in life even after the resumption of ad libitum (AL) feeding. We examined a range of metabolic parameters (body mass, body composition (lean and fat mass), glucose tolerance, fed blood glucose, fasting plasma insulin and insulin-like growth factor 1 (IGF-1), insulin sensitivity) in male C57BL/6 mice dietary switched from DR to AL (DR-AL) at 11 months of age (mid life). The converse switch (AL-DR) was also undertaken at this time. We then compared metabolic parameters of the switched mice to one another and to age-matched mice maintained exclusively on an AL or DR diet from early life (3 months of age) at 1 month, 6 months or 10 months post switch.&lt;/p&gt; &lt;p&gt;Results: Male mice dietary switched from AL-DR in mid life adopted the metabolic phenotype of mice exposed to DR from early life, so by the 10-month timepoint the AL-DR mice overlapped significantly with the DR mice in terms of their metabolic phenotype. Those animals switched from DR-AL in mid life showed clear evidence of a glycemic memory, with significantly improved glucose tolerance relative to mice maintained exclusively on AL feeding from early life. This difference in glucose tolerance was still apparent 10 months after the dietary switch, despite body mass, fasting insulin levels and insulin sensitivity all being similar to AL mice at this time.&lt;/p&gt; &lt;p&gt;Conclusions: Male C57BL/6 mice retain a long-term glycemic memory of early-life DR, in that glucose tolerance is enhanced in mice switched from DR-AL in mid life, relative to AL mice, even 10 months following the dietary switch. These data therefore indicate that the phenotypic benefits of DR are not completely dissipated following a return to AL feeding. The challenge now is to understand the molecular mechanisms underlying these effects, the time course of these effects and whether similar interventions can confer comparable benefits in humans.&lt;/p&gt

Increased Fitness of Rice Plants to Abiotic Stress Via Habitat Adapted Symbiosis: A Strategy for Mitigating Impacts of Climate Change

Climate change and catastrophic events have contributed to rice shortages in several regions due to decreased water availability and soil salinization. Although not adapted to salt or drought stress, two commercial rice varieties achieved tolerance to these stresses by colonizing them with Class 2 fungal endophytes isolated from plants growing across moisture and salinity gradients

Developmental programming: State-of-the-science and future directions-Summary from a Pennington Biomedical symposium.

OBJECTIVE: On December 8-9, 2014, the Pennington Biomedical Research Center convened a scientific symposium to review the state-of-the-science and future directions for the study of developmental programming of obesity and chronic disease. The objectives of the symposium were to discuss: (i) past and current scientific advances in animal models, population-based cohort studies, and human clinical trials, (ii) the state-of-the-science of epigenetic-based research, and (iii) considerations for future studies. RESULTS: This symposium provided a comprehensive assessment of the state of the scientific field and identified research gaps and opportunities for future research in order to understand the mechanisms contributing to the developmental programming of health and disease. CONCLUSIONS: Identifying the mechanisms which cause or contribute to developmental programming of future generations will be invaluable to the scientific and medical community. The ability to intervene during critical periods of prenatal and early postnatal life to promote lifelong health is the ultimate goal. Considerations for future research including the use of animal models, the study design in human cohorts with considerations about the timing of the intrauterine exposure, and the resulting tissue-specific epigenetic signature were extensively discussed and are presented in this meeting summary.The symposium was funded by NORC Center Grant P30DK072476 from the NIDDK. LAG is supported by T32DK064584 from the NIDDK. Work in MS Laboratory was supported by MOP‐42411 from the Canadian Institute of Health Research. Work in JAM Laboratory was supported by the Center for Nutrition Research at the University of Navarra in Pamplona, Spain. RAW is supported by a grant from the U.S. Department of Agriculture (USDA) [CRIS 3092‐5‐001‐059]. Work in BTH Laboratory was supported by the National Institutes of Health (R01AG042190) and the European Union's Seventh Framework Program IDEAL (FP7/2007‐2011; grant agreement No. 259679). Work in CL Laboratory was funded by The Swedish Research Council and The Novo Nordisk Foundation. SEO is a member of the University of Cambridge MRC Metabolic Diseases Unit. MFH is the recipient of an American Diabetes Association (ADA) Pathways To Stop Diabetes Award. Work in ER and LMR Laboratories was partially funded by a NORC grant titled “Nutritional Programming: Environmental and Molecular Interactions” to ER (P30DK072476)

Immunoregulatory gene polymorphisms in women with preeclampsia

The costimulatory molecules CD28, cytotoxic T-lymphocyte antigen-4 (CTLA-4) (cytotoxic T-lymphocyte-associated antigen-4) and inducible costimulator (ICOS) are believed to have a critical modulatory role in the immune response. However, few studies have been performed on the role of these immune regulatory molecules and their polymorphisms in women with preeclampsia (PE). the aim of our study was to evaluate the CTLA4 (+49 A/G) (rs 231775), CD28 (+17 T/C) (rs 3116496) and ICOS (-1564 T/C) (rs 4675378) gene polymorphisms in Brazilian women with PE. This case-control study included 130 patients with PE and 261 control women without any obstetric or systemic disorders. Genomic DNA was extracted from peripheral blood, and the polymorphism genotyping was performed by digesting the PCR products with the restriction endonucleases BbvI (CTLA-4), Afel (CD28) and AluI (ICOS). Data were analyzed by X(2) or Fisher's exact test; a P-value of < 0.05 was considered as significant. There were significant differences in the ICOS genotype and allelic frequencies between the PE and control groups (P=0.01 and P=0.01, respectively). We found a significantly lower frequency of the ICOS (-1564) T allele in women with mild PE compared with the controls. There were no differences in the CTLA-4 (+49 A/G) and CD28 (+17 T/C) genotypes and allelic frequencies between the PE patients and controls. Our data suggest that PE is associated with ICOS, but is not associated with the CTLA-4 or CD28 gene polymorphisms. Hypertension Research (2011) 34, 384-388; doi:10.1038/hr.2010.247; published online 16 December 2010Fundacao de Amparo a PesquisaCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de São Paulo, Dept Obstet, BR-01415002 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Obstet, BR-01415002 São Paulo, BrazilFundacao de Amparo a Pesquisa: 07/57446-0Web of Scienc