63 research outputs found

    Genetic predisposition, dietary restraint and disinhibition in relation to short and long-term weight loss

    Get PDF
    BACKGROUND: Interindividual differences in response to weight loss and maintenance thereafter are ascribed to genetic predisposition and behavioral changes. OBJECTIVE: To examine whether body weight and short and long-term body weight loss were affected by candidate single nucleotide polymorphisms (SNPs) and changes in eating behavior or by an interaction between these genetic and behavioral factors. METHODS: 150 healthy subjects (39 males, 111 females) aged 20-50y with a BMI of 27-38kg/m2 followed a very low energy diet for 8-weeks, followed by a 3-month weight maintenance period. SNPs were selected from six candidate genes: ADRB2, FTO, MC4R, PPARG, PPARD, and PPARGC1A. Changes in eating behavior were determined with the Three Factor Eating Questionnaire. RESULTS: A high genetic predisposition score was associated with a high body weight at baseline and more short-term weight loss. From the six selected obesity-related SNPs, FTO was associated with increased body weight at baseline, and the effect allele of PPARGC1A was positively associated with short-term weight loss, when assessed for each SNP separately. Long-term weight loss was associated with a larger increase in dietary restraint and larger decrease in disinhibition. CONCLUSION: During long-term weight loss, genetic effects are dominated by changes in eating behavior

    Heritability and genetic etiology of habitual physical activity: a twin study with objective measures

    Get PDF
    Twin studies with objective measurements suggest habitual physical activity (HPA) are modestly to highly heritable, depending on age. We aimed to confirm or refute this finding and identify relevant genetic variants using a candidate gene approach. HPA was measured for 14 days with a validated triaxial accelerometer (Tracmor) in two populations: (1) 28 monozygotic and 24 dizygotic same-sex twin pairs (aged 22 ± 5 years, BMI 21.8 ± 3.4 kg/m(2), 21 male, 31 female pairs); (2) 52 and 65 unrelated men and women (aged 21 ± 2 years, BMI 22.0 ± 2.5 kg/m(2)). Single nucleotide polymorphisms (SNPs) in PPARD, PPARGC1A, NRF1 and MTOR were considered candidates. Association analyses were performed for both groups separately followed by meta-analysis. Structural equation modeling shows significant familiality for HPA, consistent with a role for additive genetic factors (heritability 57 %, 95 % CI 32–74 %, AE model) or common environmental factors (47 %, 95 % CI 23–65 %, CE model). A moderate heritability was observed for the time spent on low- and high-intensity physical activity (P ≤ 0.05), but could not be confirmed for the time spent on moderate-intensity physical activity. For PPARD, each additional effect allele was inversely associated with HPA (P ≤ 0.01; rs2076168 allele C) or tended to be associated with HPA (P ≤ 0.05; rs2267668 allele G). Linkage disequilibrium existed between those two SNPs (alleles A/G and A/C, respectively) and meta-analysis showed that carriers of the AAGC haplotype were less physically active than carriers of the AAAA and AA AC haplotypes combined (P = 0.017). For PPARGC1A, carriers of AA in rs8192678 spent more time on high-intensity physical activity than GG carriers (P = 0.001). No associations were observed with SNPs in NRF1 and MTOR. In conclusion, HPA may be modestly heritable, which is confirmed by an association with variants in PPARD

    Blood profile of proteins and steroid hormones predicts weight change after weight loss with interactions of dietary protein level and glycemic index

    Get PDF
    Weight regain after weight loss is common. In the Diogenes dietary intervention study, high protein and low glycemic index (GI) diet improved weight maintenance. OBJECTIVE: To identify blood predictors for weight change after weight loss following the dietary intervention within the Diogenes study. DESIGN: Blood samples were collected at baseline and after 8-week low caloric diet-induced weight loss from 48 women who continued to lose weight and 48 women who regained weight during subsequent 6-month dietary intervention period with 4 diets varying in protein and GI levels. Thirty-one proteins and 3 steroid hormones were measured. RESULTS: Angiotensin I converting enzyme (ACE) was the most important predictor. Its greater reduction during the 8-week weight loss was related to continued weight loss during the subsequent 6 months, identified by both Logistic Regression and Random Forests analyses. The prediction power of ACE was influenced by immunoproteins, particularly fibrinogen. Leptin, luteinizing hormone and some immunoproteins showed interactions with dietary protein level, while interleukin 8 showed interaction with GI level on the prediction of weight maintenance. A predictor panel of 15 variables enabled an optimal classification by Random Forests with an error rate of 24±1%. A logistic regression model with independent variables from 9 blood analytes had a prediction accuracy of 92%. CONCLUSIONS: A selected panel of blood proteins/steroids can predict the weight change after weight loss. ACE may play an important role in weight maintenance. The interactions of blood factors with dietary components are important for personalized dietary advice after weight loss

    Cellular and molecular aspects of weight regulation: the adipose tissue

    Get PDF
    This dissertation studied the effects of a low-calorie diet on fat molecules and the impact of genes on body weight regulation. We discovered two different genetic variations (the FTO gene in men and the MMP2 gene in women) that predict a weight gain of at least 8 kilos over the course of a decade. Furthermore, it was shown that fat cells increase their ability to include higher levels of glucose and fatty acids following weight loss achieved with a diet. After three weeks, fat cells were found to be craving fat, a mechanism provoking old eating habits (the so-called yo-yo effect). Certain target groups, including people having a genetic predisposition, should therefore receive improved weight-loss and/or weight-maintenance counselling

    Generally detected proteins in comparative proteomics--a matter of cellular stress response?

    No full text
    The specificity of proteins identified by proteomics as biomarkers for defined conditions or as components of biological processes and pathways is crucial. We critically reviewed differentially expressed proteins from comparative proteomic studies identified by 2-DE followed by MS, especially with MALDI technique. Based on 66 of those studies, a list of 44 proteins is presented as generally detected proteins regardless of species, in vivo or in vitro conditions, tissues and organs, and experimental objective. Similarly, a list of 28 generally detected protein families is presented. The enriched functions linked to these generally detected proteins reveal that there are some common biological features beyond the technical limitations. Cellular stress response can be the universal reason as to why these proteins are generally expressed differentially. Using those proteins as biomarkers for cellular processes other than stress response should be done with caution. In future proteomic studies more profound approaches should be applied to look beyond these proteins to find specific biomarkers. Our results are discussed in relation to a recent viewpoint publication by Petrak et al. [Proteomics 2008, 8, 1744-1749]

    Glutamine regulates the expression of proteins with a potential health-promoting effect in human intestinal Caco-2 cells

    No full text
    Glutamine is an essential amino acid for the enterocytes with respect to maintaining the gut mucosal integrity and function. This study was conducted to explore a molecular basis for the beneficial effects of glutamine on intestinal cells by searching for glutamine-dependent changes in the proteome. Caco-2 cells were exposed to different concentrations of L-glutamine with or without L-methionine sulfoximine, an inhibitor of the glutamine synthetase activity. 2-DE combined with MALDI-TOF-MS was used to identify proteins whose expression is changed by glutamine. To assess the relative protein synthesis rate, incorporation of L-[2H5]glutamine into individual proteins was monitored. The expression levels of 14 proteins changed significantly with the glutamine availability. Examples of differentially expressed proteins with potential health-promoting effects on the intestine are plasma retinol-binding protein, ornithine aminotransferase, apolipoprotein A-I, mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase, and acyl-CoA synthetase 5. Expression of these proteins was not changed by arginine deprivation. The differential change in the expression levels of the proteins was not correlated with their rate of synthesis, excluding an effect of glutamine depletion on general protein synthesis. Together, this study shows a gene-specific effect of glutamine on intestinal cell

    Differentiation stage-dependent preferred uptake of basolateral (systemic) glutamine into Caco-2 cells results in its accumulation in proteins with a role in cell-cell interaction

    No full text
    Glutamine is an essential amino acid for enterocytes, especially in states of critical illness and injury. In several studies it has been speculated that the beneficial effects of glutamine are dependent on the route of supply (luminal or systemic). The aim of this study was to investigate the relevance of both routes of glutamine delivery to in vitro intestinal cells and to explore the molecular basis for proposed beneficial glutamine effects: (a) by determining the relative uptake of radiolabelled glutamine in Caco-2 cells; (b) by assessing the effect of glutamine on the proteome of Caco-2 cells using a 2D gel electrophoresis approach; and (c) by examining glutamine incorporation into cellular proteins using a new mass spectrometry-based method with stable isotope labelled glutamine. Results of this study show that exogenous glutamine is taken up by Caco-2 cells from both the apical and the basolateral side. Basolateral uptake consistently exceeds apical uptake and this phenomenon is more pronounced in 5-day-differentiated cells than in 15-day-differentiated cells. No effect of exogenous glutamine supply on the proteome was detected. However, we demonstrated that exogenous glutamine is incorporated into newly synthesized proteins and this occurred at a faster rate from basolateral glutamine, which is in line with the uptake rates. Interestingly, a large number of rapidly labelled proteins is involved in establishing cell-cell interactions. In this respect, our data may point to a molecular basis for observed beneficial effects of glutamine on intestinal cells and support results from studies with critically ill patients where parenteral glutamine supplementation is preferred over luminal supplementation
    • …
    corecore