Dietary Strategies for Weight Loss Maintenance.

Weight regain after a successful weight loss intervention is very common. Most studies show that, on average, the weight loss attained during a weight loss intervention period is not or is not fully maintained during follow-up. We review what is currently known about dietary strategies for weight loss maintenance, focusing on nutrient composition by means of a systematic review and meta-analysis of studies and discuss other potential strategies that have not been studied so far. Twenty-one studies with 2875 participants who were overweight or obese are included in this systematic review and meta-analysis. Studies investigate increased protein intake (12 studies), lower dietary glycemic index (four studies), green tea (three studies), conjugated linoleic acid (three studies), higher fibre intake (three studies), and other miscellaneous interventions (six studies). The meta-analysis shows a significant beneficial effect of higher protein intake on the prevention of weight regain (SMD (standardized mean difference) -0.17 (95% CI -0.29, -0.05), z = 2.80, p = 0.005), without evidence for heterogeneity among the included studies. No significant effect of the other strategies is detected. Diets that combine higher protein intake with different other potentially beneficial strategies, such as anti-inflammatory or anti-insulinemic diets, may have more robust effects, but these have not been tested in randomized clinical trials yet.

Extreme obesity is associated with variation in genes related to the circadian rhythm of food intake and hypothalamic signaling.

The hypothalamus is important for regulation of energy intake. Mutations in genes involved in the function of the hypothalamus can lead to early-onset severe obesity. To look further into this, we have followed a strategy that allowed us to identify rare and common gene variants as candidates for the background of extreme obesity from a relatively small cohort. For that we focused on subjects with a well-selected phenotype and on a defined gene set and used a rich source of genetic data with stringent cut-off values. A list of 166 genes functionally related to the hypothalamus was generated. In those genes complete exome sequence data from 30 extreme obese subjects (60 genomes) were screened for novel rare indel, nonsense, and missense variants with a predicted negative impact on protein function. In addition, (moderately) common variants in those genes were analyzed for allelic association using the general population as reference (false discovery rate<0.05). Six novel rare deleterious missense variants were found in the genes for BAIAP3, NBEA, PRRC2A, RYR1, SIM1, and TRH, and a novel indel variant in LEPR. Common variants in the six genes for MBOAT4, NPC1, NPW, NUCB2, PER1, and PRRC2A showed significant allelic association with extreme obesity. Our findings underscore the complexity of the genetic background of extreme obesity involving rare and common variants of genes from defined metabolic and physiologic processes, in particular regulation of the circadian rhythm of food intake and hypothalamic signaling.

The role of catechol-O-methyl transferase Val(108/158)Met polymorphism (rs4680) in the effect of green tea on resting energy expenditure and fat oxidation: a pilot study.

INTRODUCTION: Green tea(GT) is able to increase energy expenditure(EE) and fat oxidation(FATox) via inhibition of catechol-O-methyl transferase(COMT) by catechins. However, this does not always appear unanimously because of large inter-individual variability. This may be explained by different alleles of the functional COMT Val108/158Met polymorphism that are associated with COMT enzyme activity; high-activity enzyme, COMT(H)(Val/Val genotype), and low-activity COMT(L)(Met/Met genotype). METHODS: Fourteen Caucasian subjects (BMI: 22.2±2.3 kg/m2, age: 21.4±2.2 years) of whom 7 with the COMT(H)-genotype and 7 with the COMT(L)-genotype were included in a randomized, cross-over study in which EE and substrate oxidation were measured with a ventilated-hood system after decaffeinated GT and placebo(PL) consumption. RESULTS: At baseline, EE, RQ, FATox and carbohydrate oxidation(CHOox) did not differ between groups. Significant interactions were observed between COMT genotypes and treatment for RQ, FATox and CHOox (p<0.05). After GT vs. PL, EE(GT: 62.2 vs. PL: 35.4 kJ.3.5 hrs; p<0.01), RQ(GT: 0.80 vs. PL: 0.83; p<0.01), FATox(GT: 18.3 vs. PL: 15.3 g/d; p<0.001) and CHOox(GT: 18.5 vs. PL: 24.3 g/d; p<0.001) were significantly different for subjects carrying the COMT(H) genotype, but not for subjects carrying the COMT(L) genotype (EE, GT: 60.3 vs. PL: 51.7 kJ.3.5 hrs; NS), (RQ, GT: 0.81 vs. PL: 0.81; NS), (FATox, GT: 17.3 vs. PL: 17.0 g/d; NS), (CHOox, GT: 22.1 vs. PL: 21.4 g/d; NS). CONCLUSION: Subjects carrying the COMT(H) genotype increased energy expenditure and fat-oxidation upon ingestion of green tea catechins vs, placebo, whereas COMT(L) genotype carriers reacted similarly to GT and PL ingestion. The differences in responses were due to the different responses on PL ingestion, but similar responses to GT ingestion, pointing to different mechanisms. The different alleles of the functional COMT Val108/158Met polymorphism appear to play a role in the inter-individual variability for EE and FATox after GT treatment. TRIAL REGISTRATION: Nederlands Trial register NTR1918.

Integrated visualization of a multi-omics study of starvation in mouse intestine.

Our understanding of complex biological processes can be enhanced by combining different kinds of high-throughput experimental data, but the use of incompatible identifiers makes data integration a challenge. We aimed to improve methods for integrating and visualizing different types of omics data. To validate these methods, we applied them to two previous studies on starvation in mice, one using proteomics and the other using transcriptomics technology. We extended the PathVisio software with new plugins to link proteins, transcripts and pathways. A low overall correlation between proteome and transcriptome data was detected (Spearman rank correlation: 0.21). At the level of individual genes, correlation was highly variable. Many mRNA/protein pairs, such as fructose biphosphate aldolase B and ATP Synthase, show good correlation. For other pairs, such as ferritin and elongation factor 2, an interesting effect is observed, where mRNA and protein levels change in opposite directions, suggesting they are not primarily regulated at the transcriptional level. We used pathway diagrams to visualize the integrated datasets and found it encouraging that transcriptomics and proteomics data supported each other at the pathway level. Visualization of the integrated dataset on pathways led to new observations on gene-regulation in the response of the gut to starvation. Our methods are generic and can be applied to any multi-omics study. The PathVisio software can be obtained at http://www.pathvisio.org. Supplemental data are available at http://www.bigcat.unimaas.nl/data/jib-supplemental/ , including instructions on reproducing the pathway visualizations of this manuscript.

Adipophilin protein expression in muscle--a possible protective role against insulin resistance.

Adipophilin is a 50 kDa protein that belongs to the PAT family (perilipin, adipophilin, TIP47, S3-12 and OXPAT), which comprises proteins involved in the coating of lipid droplets. Little is known about the functional role of adipophilin in muscle. Using the C2C12 cell line as a model, we demonstrate that palmitic acid-treated cells highly express the adipophilin protein in a dose-dependent way. Next, we show that oleic acid is a more potent inducer of adipophilin protein levels than palmitic acid. Cells treated with oleic acid have a higher adipophilin protein expression and higher triglyceride levels but less impairment of insulin signaling than cells treated with palmitic acid. Additionally, we show that peroxisome proliferator-activated receptor (PPAR)alpha, PPARbeta/delta and PPARgamma agonists all increase the expression of the adipophilin protein in C2C12 cells. This effect was most pronounced for the PPARalpha agonist GW7647. Furthermore, the expression of adipophilin as a 37 kDa N-terminally truncated protein is higher in the gastrocnemius than in the quadriceps of C57BL/6J mice, especially after an 8-week high-fat diet. The expression of adipophilin was higher in the muscle of mice fed a 4-week high-fat diet based on olive oil or safflower oil than in mice fed a 4-week high-fat diet based on palm oil. After 2 weeks of intervention, plasma glucose, plasma insulin and the homeostasis model assessment of insulin resistance index were lower in mice fed a 4-week high-fat diet based on olive oil or safflower oil than in mice fed a 4-week high-fat diet based on palm oil. Taken together, the results obtained in the present study indicate that adipophilin protein expression in muscle is involved in maintaining insulin sensitivity.

Differentiated CaCo-2 cells as an in-vitro model to evaluate de-novo apolipoprotein A-I production in the small intestine.

BACKGROUND: Increasing HDL cholesterol concentrations by stimulating de-novo apolipoprotein A-I (apoA-I) production in the liver and/or in the small intestine is a potential strategy to reduce coronary heart disease risk. Although there is quite some knowledge concerning regulatory effects in the liver, less is known concerning potential agents that could elevate de-novo apoA-I production in the small intestine. METHODS: Therefore, we compared side-by-side effects of various peroxisome proliferator-activated receptor (PPAR)alpha, PPARgamma, retinoid-X-receptor alpha, and farnesoid-X-receptor agonists on de-novo apoA-I production in differentiated CaCo-2 and HepG2 cells. RESULTS: For PPARa agonists, we showed that GW7647 elevated apoA-I concentrations in the medium of both cell models, whereas WY14643 elevated only de-novo apoA-I concentrations in differentiated CaCo-2 cells. Unexpectedly, fenofibric acid lowered apoA-I medium concentrations in both cell lines, which could not be explained by a lack of PPAR transactivation or a lack of retinoid-X-receptor a activation. For farnesoid-X-receptor agonists, chenodeoxycholic acid strongly reduced apoA-I concentrations both in differentiated CaCo-2 and HepG2 cells, whereas GW4064 and taurocholate only lowered apoA-I in CaCo-2 cells (GW4064) or in HepG2 cells (taurocholate). However, overall effects of all individual components on apoA-I production in differentiated CaCo-2 and HepG2 cells were highly correlated (r = 0.68; P = 0.037; N=9). CONCLUSION: We conclude that differentiated CaCo-2 cells are suitable models to study de-novo small intestinal apoA-I production in vitro enabling the possibility to screen for potential bioactive dietary components. This cell model may also determine small-intestinal-specific effects, as some discrepancy was found between both cell models.

Arginine deficiency in preconfluent intestinal Caco-2 cells modulates expression of proteins involved in proliferation, apoptosis, and heat shock response.

Arginine is classified as a conditionally essential amino acid required exogenously during catabolic disease states and periods of rapid growth, both characterized by increased arginine utilization. Arginine plays an important role in the intestine, where it is extensively metabolized, and enhances its immune-supportive function and mucosal repair. Cell proliferation is important for the latter process. This study aimed for a better molecular insight in the response to arginine deprivation/supplementation of preconfluent and 5-day-confluent, differentiated Caco-2 intestinal cells. The potential of citrulline to counteract the effects of arginine deprivation was investigated in preconfluent cells. 2-DE combined with MALDI-TOF-MS and the antibody microarray technology were applied. Evidence is provided that arginine deficiency modulates the protein expression profiles of preconfluent Caco-2 cells differently than that of postconfluent differentiated cells. In preconfluent cells, certain proteins changed in direct response to arginine deficiency, whereas other proteins did not, but instead responded during the recovery phase after an arginine/citrulline resupplementation. The protein changes suggest that arginine deprivation decreases cell proliferation and heat shock protein expression, and enhances the cells susceptibility to apoptosis. These processes are critical for proper cell function, and hence a state of arginine deficiency can be detrimental for intestinal cells which proliferate actively in vivo.

Phenotype of the neural tube defect mouse model bent tail is not sensitive to maternal folinic acid, myo-inositol, or zinc supplementation.

BACKGROUND: Bent tail is a mouse model for X-linked neural tube defects (NTDs) that is characterized by the presence of exencephaly, a delayed posterior neuropore closure, and a tail phenotype. In addition, Bent tail shows laterality defects and increased prenatal mortality. The congenital malformations of this mouse are caused by a submicroscopic deletion that completely encompasses the gene coding for the zinc finger transcription factor Zic3. In this study we investigated the sensitivity of the phenotype of Bent tail to the nutrients folinic acid, myo-inositol, and zinc. These nutrients are thought to be involved in the etiology of NTDs, in combination with a genetic predisposition. METHODS: The most penetrant phenotype of the Bent tail mouse, the tail malformation, was used as a marker for the nutrient sensitivity of the neural phenotype. The size of the litters and the survival of the offspring, subdivided according to genotype, were analyzed as markers for the nutrient sensitivity of other phenotypic features of Bent tail. RESULTS: In confirmation of earlier studies, we observed the prenatal loss of a number of homozygous females and hemizygous males, as well as the effect of genotype on the tail phenotype of Bent tail. However, periconceptional supplementation of the maternal diet with folinic acid, myo-inositol, or zinc produced no significant effects on either the tail phenotype of the offspring or the size and genotypic composition of the litters. CONCLUSIONS: Bent tail appears to be a folinic acid-, myo-inositol-, and zinc-insensitive mouse model for NTDs.