Physiogenomic analysis of weight loss induced by dietary carbohydrate restriction

BACKGROUND: Diets that restrict carbohydrate (CHO) have proven to be a successful dietary treatment of obesity for many people, but the degree of weight loss varies across individuals. The extent to which genetic factors associate with the magnitude of weight loss induced by CHO restriction is unknown. We examined associations among polymorphisms in candidate genes and weight loss in order to understand the physiological factors influencing body weight responses to CHO restriction. METHODS: We screened for genetic associations with weight loss in 86 healthy adults who were instructed to restrict CHO to a level that induced a small level of ketosis (CHO ~10% of total energy). A total of 27 single nucleotide polymorphisms (SNPs) were selected from 15 candidate genes involved in fat digestion/metabolism, intracellular glucose metabolism, lipoprotein remodeling, and appetite regulation. Multiple linear regression was used to rank the SNPs according to probability of association, and the most significant associations were analyzed in greater detail. RESULTS: Mean weight loss was 6.4 kg. SNPs in the gastric lipase (LIPF), hepatic glycogen synthase (GYS2), cholesteryl ester transfer protein (CETP) and galanin (GAL) genes were significantly associated with weight loss. CONCLUSION: A strong association between weight loss induced by dietary CHO restriction and variability in genes regulating fat digestion, hepatic glucose metabolism, intravascular lipoprotein remodeling, and appetite were detected. These discoveries could provide clues to important physiologic adaptations underlying the body mass response to CHO restriction

Physiogenomic comparison of human fat loss in response to diets restrictive of carbohydrate or fat

<p>Abstract</p> <p>Background</p> <p>Genetic factors that predict responses to diet may ultimately be used to individualize dietary recommendations. We used physiogenomics to explore associations among polymorphisms in candidate genes and changes in relative body fat (Δ%BF) to low fat and low carbohydrate diets.</p> <p>Methods</p> <p>We assessed Δ%BF using dual energy X-ray absorptiometry (DXA) in 93 healthy adults who consumed a low carbohydrate diet (carbohydrate ~12% total energy) (LC diet) and in 70, a low fat diet (fat ~25% total energy) (LF diet). Fifty-three single nucleotide polymorphisms (SNPs) selected from 28 candidate genes involved in food intake, energy homeostasis, and adipocyte regulation were ranked according to probability of association with the change in %BF using multiple linear regression.</p> <p>Results</p> <p>Dieting reduced %BF by 3.0 ± 2.6% (absolute units) for LC and 1.9 ± 1.6% for LF (p < 0.01). SNPs in nine genes were significantly associated with Δ%BF, with four significant after correction for multiple statistical testing: rs322695 near the retinoic acid receptor beta (<it>RARB</it>) (p < 0.005), rs2838549 in the hepatic phosphofructokinase (<it>PFKL</it>), and rs3100722 in the histamine N-methyl transferase (<it>HNMT</it>) genes (both p < 0.041) due to LF; and the rs5950584 SNP in the angiotensin receptor Type II (<it>AGTR2</it>) gene due to LC (p < 0.021).</p> <p>Conclusion</p> <p>Fat loss under LC and LF diet regimes appears to have distinct mechanisms, with <it>PFKL </it>and <it>HNMT </it>and <it>RARB </it>involved in fat restriction; and <it>AGTR2 </it>involved in carbohydrate restriction. These discoveries could provide clues to important physiologic mechanisms underlying the Δ%BF to low carbohydrate and low fat diets.</p

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Die Gruppe der Nickelbasis Superlegierungen zählt im Hinblick auf Hochtemperaturfestigkeit und Oxidations- bzw. Korrosionsbeständigkeit zu den am weitesten entwickelten Legierungen. Sie kommen in erster Linie als Schaufelmaterial in der Verbrennungssektion von stationären Industriegasturbinen und Flugturbinen zum Einsatz. Durch die Entwicklung neuer Vakuumfeingießverfahren konnte ihr Eigenschaftsprofil weiter optimiert werden. Ziel dieser Arbeit war die Erfassung der Hochtemperatureigenschaften einer neu entwickelten stängelkristallin erstarrten rheniumhaltigen Legierung. Hierbei wurde besonderes Augenmerk auf den Einfluss des Legierungselements Rhenium und der damit verbundenen segregationsbedingten Sprödphasenbildung gelegt. Die Untersuchungen zeigten eine deutliche Überlegenheit der Hochtemperaturfestigkeit gegenüber konventionellen rheniumfreien Legierungen. Dieser Festigkeitsgewinn ermöglicht eine um 25 K erhöhte Gaseintrittstemperatur in der Turbine, wodurch die Effizienz des Aggregats gesteigert und die Schadstoffemission von NOx und CO2 reduziert wird. Durch eine bruchmechanische Betrachtung konnte das schädigende Verhalten der Sprödphasen geklärt werden. Die Untersuchung der Rheniumverteilung im dendritischen Gefüge lieferte einen Ansatz zur modellmäßigen Beschreibung der Rheniumdiffusion.Nickel based superalloys are the most advanced alloys regarding high temperature mechanical properties, oxidation and hot corrosion resistance. Due to these capabilities nickel based superalloys are widely used as blade material for the combustion section of industrial gas turbines and flight turbines. Optimised investment casting techniques lead to improved material properties. Aim of this work was to determine static and dynamic properties at high temperatures of a newly developed directionally solidified superalloy. Main issue of the investigation was the influence of the alloying element rhenium. Creep rupture tests revealed superior creep rupture life compared to that of rhenium free alloys. Thus the gas inlet temperature in increased by 25 K causing improved efficiency and reduction of emission of NOx and CO2. The deleterious behaviour of TCP phases could be explained by using stress intensity theory. A model to calculate rhenium interdiffusion within the dendritic DS-structure was suggested by using results of rhenium distribution measurements

Erstarrungsmikrostruktur und Hochtemperatureigenschaften rheniumhaltiger, stängelkristalliner Nickel-Basis-Superlegierungen

Nickel based superalloys are the most advanced alloys regarding high temperature mechanical properties, oxidation and hot corrosion resistance. Due to these capabilities nickel based superalloys are widely used as blade material for the combustion section of industrial gas turbines and flight turbines. Optimised investment casting techniques lead to improved material properties. Aim of this work was to determine static and dynamic properties at high temperatures of a newly developed directionally solidified superalloy. Main issue of the investigation was the influence of the alloying element rhenium. Creep rupture tests revealed superior creep rupture life compared to that of rhenium free alloys. Thus the gas inlet temperature in increased by 25 K causing improved efficiency and reduction of emission of NOx and CO2. The deleterious behaviour of TCP phases could be explained by using stress intensity theory. A model to calculate rhenium interdiffusion within the dendritic DS-structure was suggested by using results of rhenium distribution measurements.Die Gruppe der Nickelbasis Superlegierungen zählt im Hinblick auf Hochtemperaturfestigkeit und Oxidations- bzw. Korrosionsbeständigkeit zu den am weitesten entwickelten Legierungen. Sie kommen in erster Linie als Schaufelmaterial in der Verbrennungssektion von stationären Industriegasturbinen und Flugturbinen zum Einsatz. Durch die Entwicklung neuer Vakuumfeingießverfahren konnte ihr Eigenschaftsprofil weiter optimiert werden. Ziel dieser Arbeit war die Erfassung der Hochtemperatureigenschaften einer neu entwickelten stängelkristallin erstarrten rheniumhaltigen Legierung. Hierbei wurde besonderes Augenmerk auf den Einfluss des Legierungselements Rhenium und der damit verbundenen segregationsbedingten Sprödphasenbildung gelegt. Die Untersuchungen zeigten eine deutliche Überlegenheit der Hochtemperaturfestigkeit gegenüber konventionellen rheniumfreien Legierungen. Dieser Festigkeitsgewinn ermöglicht eine um 25 K erhöhte Gaseintrittstemperatur in der Turbine, wodurch die Effizienz des Aggregats gesteigert und die Schadstoffemission von NOx und CO2 reduziert wird. Durch eine bruchmechanische Betrachtung konnte das schädigende Verhalten der Sprödphasen geklärt werden. Die Untersuchung der Rheniumverteilung im dendritischen Gefüge lieferte einen Ansatz zur modellmäßigen Beschreibung der Rheniumdiffusion

Effect of grain boundary characteristics on hot tearing in directional solidification of superalloys

The effect of grain boundary (GB) misorientation on hot tearing susceptibility of directionally solidified (DS) nickel-based superalloys was explored. We found that the castability of second generation nickel-based superalloy CMSX-4 is inferior to DS superalloy IN792, an alloy well known for bad castability. The castability of CMSX-4 is somewhat improved at a higher solidification rate. The hot tearing tendency increases with increasing GB misorientation angle. As feeding tendency becomes greater with increasing misorientation, this points to the importance of GB cohesion for solidification cracking in the alloy. Microstructure investigation reveals that hot tearing is associated with formation of continuous gamma and gamma prime eutectic films at the GB in CMSX-4. We assume that the gamma and gamma prime eutectic, which reflects the remaining liquid at the end of solidification, prevents the impinging dendrite arms from touching and in this way decreases cohesion

Distribution of baseline and change in percent body fat for LF (top) and LC (bottom) groups

The vertical axes () indicates the number of patients observed within a given 10% interval up to 60% (baseline, left panels) or within a given 2% or 5% interval (change, right panels) on the horizontal axes. Genotyping was not completed in 3 LF subjects and 7 LC subjects.<p><b>Copyright information:</b></p><p>Taken from "Physiogenomic comparison of human fat loss in response to diets restrictive of carbohydrate or fat"</p><p>http://www.nutritionandmetabolism.com/content/5/1/4</p><p>Nutrition & Metabolism 2008;5():4-4.</p><p>Published online 6 Feb 2008</p><p>PMCID:PMC2270845.</p><p></p

Physiogenomic representation of the most significant genetic associations found in the low carbohydrate group

See Figure 2 legend for details regarding individual patient genotypes (), the distribution of Δ%BF (), and the LOESS fit of the allele frequency () as a function of Δ%BF.<p><b>Copyright information:</b></p><p>Taken from "Physiogenomic comparison of human fat loss in response to diets restrictive of carbohydrate or fat"</p><p>http://www.nutritionandmetabolism.com/content/5/1/4</p><p>Nutrition & Metabolism 2008;5():4-4.</p><p>Published online 6 Feb 2008</p><p>PMCID:PMC2270845.</p><p></p