Gastric bypass surgery reveals independency of obesity and diabetes melitus type 2

Background

Roux-en-Y gastric bypass surgery is widely applied to ameliorate morbid obesity, including diabetes in people with type 2 diabetes. The latter vanish a few days after surgery for many, but not in all patients before any weight reduction has occurred. The explanation for this change in metabolic status is poorly understood, but the observation may suggest that the fate obesity and diabetes is only partly linked after surgery.

Methods

The trajectories of weight reduction measured as reduced body mass index (BMI) in 741obese subjects with and without diabetes were evaluated. Evaluation was performed on three groups: 1) subjects that were non-diabetic before and after surgery; 2) subjects that were diabetics before surgery but non-diabetics after surgery; and 3) subjects that were diabetics before surgery and remained diabetics after surgery. The diabetic state was established at HbA1c above 48 mmol/mol.

Results

The trajectories differ significantly between groups and any sub-populations of groups, the latter identified by the distance between individual trajectories using a k-means procedure. The results suggest that different domains in the enormous genetic network governing basic metabolism are perturbed in obesity and diabetes, and in fact some of the patients are affected by two distinct diseases: obesity and diabetes mellitus type 2.

Conclusion

Although RYGB “normalized” many glycaemic parameters in some of the diabetic subjects apparently converting to a non-diabetics state, other diabetic subjects stay diabetic in the context of the new gut anatomy after surgery. Thus, the obesity part of the glycaemic derangement may have been ameliorated, but some defects of the diabetic state had not.

     

Thermoduric and Psychrotrophic Organisms on Poorly Cleansed Milking Plants and Farm Bulk Milk Tanks

S ummary . Poorly cleansed pipeline milking plants gave much higher total and thermoduric colony counts than the internal surfaces of refrigerated farm bulk milk tanks, higher counts being recorded for milking plants after circulation cleaning than after cleansing by the acidified boiling water (ABW) method. Psychrotrophic counts were highest for farm milk tanks and lowest for milking plants cleansed by the ABW method. There was much variation in the proportion of thermoduric and psychrotrophic organisms in the total bacterial content of milking plants determined at 30°, thermodurics being much more prevalent in 21% of the rinses and psychrotrophs in 16%. Both groups formed about equal proportions in 9% of the pipeline rinses. The bacterial content of the farm bulk milk tanks was characterized by many psychrotrophs and few thermodurics.     

Major shifts in gut microbiota during development and its relationship to growth in ostriches

The development of gut microbiota during ontogeny is emerging as an important process influencing physiology, immunity and fitness in vertebrates. However, knowledge of how bacteria colonize the juvenile gut, how this is influenced by changes in the diversity of gut bacteria and to what extent this influences host fitness, particularly in nonmodel organisms, is lacking. Here we used 16S rRNA gene sequencing to describe the successional development of the faecal microbiome in ostriches (Struthio camelus, n = 66, repeatedly sampled) over the first 3 months of life and its relationship to growth. We found a gradual increase in microbial diversity with age that involved multiple colonization and extinction events and a major taxonomic shift in bacteria that coincided with the cessation of yolk absorption. Comparisons with the microbiota of adults (n = 5) revealed that the chicks became more similar in their microbial diversity and composition to adults as they aged. There was a five‐fold difference in juvenile growth during development, and growth during the first week of age was strongly positively correlated with the abundance of the genus Bacteroides and negatively correlated with Akkermansia. After the first week, the abundances of six phylogenetically diverse families (Peptococcaceae, S24‐7, Verrucomicrobiae, Anaeroplasmataceae, Streptococcaceae, Methanobacteriaceae) were associated with subsequent reductions in chick growth in an age‐specific and transient manner. These results have broad implications for our understanding of the development of gut microbiota and its associations with animal growth.     

A multivariate screening strategy for investigating metabolic effects of strenuous physical exercise in human serum

A novel hypothesis-free multivariate screening methodology for the study of human exercise metabolism in blood serum is presented. Serum gas chromatography/time-of-flight mass spectrometry (GC/TOFMS) data was processed using hierarchical multivariate curve resolution (H-MCR), and orthogonal partial least-squares discriminant analysis (OPLS-DA) was used to model the systematic variation related to the acute effect of strenuous exercise. Potential metabolic biomarkers were identified using data base comparisons. Extensive validation was carried out including predictive H-MCR, 7-fold full cross-validation, and predictions for the OPLS-DA model, variable permutation for highlighting interesting metabolites, and pairwise t tests for examining the significance of metabolites. The concentration changes of potential biomarkers were verified in the raw GC/TOFMS data. In total, 420 potential metabolites were resolved in the serum samples. On the basis of the relative concentrations of the 420 resolved metabolites, a valid multivariate model for the difference between pre- and post-exercise subjects was obtained. A total of 34 metabolites were highlighted as potential biomarkers, all statistically significant (p < 8.1E-05). As an example, two potential markers were identified as glycerol and asparagine. The concentration changes for these two metabolites were also verified in the raw GC/TOFMS data.The strategy was shown to facilitate interpretation and validation of metabolic interactions in human serum as well as revealing the identity of potential markers for known or novel mechanisms of human exercise physiology. The multivariate way of addressing metabolism studies can help to increase the understanding of the integrative biology behind, as well as unravel new mechanistic explanations in relation to, exercise physiology.     

Reliable profile detection in comparative metabolomics

A strategy for processing of metabolomic GC/MS data is presented. By considering the relationship between quantity and quality of detected profiles, representative data suitable for multiple sample comparisons and metabolite identification was generated. Design of experiments (DOE) and multivariate analysis was used to relate the changes in settings of the hierarchical multivariate curve resolution (H-MCR) method to quantitative and qualitative characteristics of the output data. These characteristics included number of resolved profiles, chromatographic quality in terms of reproducibility between analytical replicates, and spectral quality defined by purity and number of spectra containing structural information. The strategy was exemplified in two datasets: one containing 119 common metabolites, 18 of which were varied according to a DOE protocol; and one consisting of rat urine samples from control rats and rats exposed to a liver toxin. It was shown that the performance of the data processing could be optimized to produce metabolite data of high quality that allowed reliable sample comparisons and metabolite identification. This is a general approach applicable to any type of data processing where the important processing parameters are known and relevant output data characteristics can be defined. The results imply that this type of data quality optimization should be carried out as an integral step of data processing to ensure high quality data for further modeling and biological evaluation. Within metabolomics, this degree of optimization will be of high importance to generate models and extract biomarkers or biomarker patterns of biological or clinical relevance.     

Assigning Membrane Binding Geometry of Cytochrome c by Polarized Light Spectroscopy

In this work we demonstrate how polarized light absorption spectroscopy (linear dichroism (LD)) analysis of the peptide ultraviolet-visible spectrum of a membrane-associated protein (cytochrome (cyt) c) allows orientation and structure to be assessed with quite high accuracy in a native membrane environment that can be systematically varied with respect to lipid composition. Cyt c binds strongly to negatively charged lipid bilayers with a distinct orientation in which its α-helical segments are on average parallel to the membrane surface. Further information is provided by the LD of the π-π^∗ transitions of the heme porphyrin and transitions of aromatic residues, mainly a single tryptophan. A good correlation with NMR data was found, and combining NMR structural data with LD angular data allowed the whole protein to be docked to the lipid membrane. When the redox state of cyt c was changed, distinct variations in the LD spectrum of the heme Soret band were seen corresponding to changes in electronic transition energies; however, no significant change in the overall protein orientation or structure was observed. Cyt c is known to interact in a specific manner with the doubly negatively charged lipid cardiolipin, and incorporation of this lipid into the membrane at physiologically relevant levels was indeed found to affect the protein orientation and its α-helical content. The detail in which cyt c binding is described in this study shows the potential of LD spectroscopy using shear-deformed lipid vesicles as a new methodology for exploring membrane protein structure and orientation.