Metabolomic Profiles of Body Mass Index in the Framingham Heart Study Reveal Distinct Cardiometabolic Phenotypes

Background

Although obesity and cardiometabolic traits commonly overlap, underlying pathways remain incompletely defined. The association of metabolite profiles across multiple cardiometabolic traits may lend insights into the interaction of obesity and metabolic health. We sought to investigate metabolic signatures of obesity and related cardiometabolic traits in the community using broad-based metabolomic profiling.

Methods and Results

We evaluated the association of 217 assayed metabolites and cross-sectional as well as longitudinal changes in cardiometabolic traits among 2,383 Framingham Offspring cohort participants. Body mass index (BMI) was associated with 69 of 217 metabolites (P<0.00023 for all), including aromatic (tyrosine, phenylalanine) and branched chain amino acids (valine, isoleucine, leucine). Additional metabolic pathways associated with BMI included the citric acid cycle (isocitrate, alpha-ketoglutarate, aconitate), the tryptophan pathway (kynurenine, kynurenic acid), and the urea cycle. There was considerable overlap in metabolite profiles between BMI, abdominal adiposity, insulin resistance [IR] and dyslipidemia, modest overlap of metabolite profiles between BMI and hyperglycemia, and little overlap with fasting glucose or elevated blood pressure. Metabolite profiles were associated with longitudinal changes in fasting glucose, but the involved metabolites (ornithine, 5-HIAA, aminoadipic acid, isoleucine, cotinine) were distinct from those associated with baseline glucose or other traits. Obesity status appeared to “modify” the association of 9 metabolites with IR. For example, bile acid metabolites were strongly associated with IR among obese but not lean individuals, whereas isoleucine had a stronger association with IR in lean individuals.

Conclusions

In this large-scale metabolite profiling study, body mass index was associated with a broad range of metabolic alterations. Metabolite profiling highlighted considerable overlap with abdominal adiposity, insulin resistance, and dyslipidemia, but not with fasting glucose or blood pressure traits.     

Targeted drug delivery of magnetic microbubble for abdominal aortic aneurysm: an in silico study

Biomechanics and Modeling in Mechanobiology - Targeted drug delivery (TDD) to abdominal aortic aneurysm (AAA) using a controlled and efficient approach has recently been a significant challenge. In...     

Human pathogens utilize host extracellular matrix proteins laminin and collagen for adhesion and invasion of the host

Laminin (Ln) and collagen are multifunctional glycoproteins that play an important role in cellular morphogenesis, cell signalling, tissue repair and cell migration. These proteins are ubiquitously present in tissues as a part of the basement membrane (BM), constitute a protective layer around blood capillaries and are included in the extracellular matrix (ECM). As a component of BMs, both Lns and collagen(s), thus function as major mechanical containment molecules that protect tissues from pathogens. Invasive pathogens breach the basal lamina and degrade ECM proteins of interstitial spaces and connective tissues using various ECM-degrading proteases or surface-bound plasminogen and matrix metalloproteinases recruited from the host. Most pathogens associated with the respiratory, gastrointestinal, or urogenital tracts, as well as with the central nervous system or the skin, have the capacity to bind and degrade Lns and collagen(s) in order to adhere to and invade host tissues. In this review, we focus on the adaptability of various pathogens to utilize these ECM proteins as enhancers for adhesion to host tissues or as a targets for degradation in order to breach the cellular barriers. The major pathogens discussed are Streptococcus, Staphylococcus, Pseudomonas, Salmonella, Yersinia, Treponema, Mycobacterium, Clostridium, Listeria, Porphyromonas and Haemophilus; Candida, Aspergillus, Pneumocystis, Cryptococcus and Coccidioides; Acanthamoeba, Trypanosoma and Trichomonas; retrovirus and papilloma virus.     

Effects of inclusion of neutral detergent soluble fibre sources in diets varying in forage particle size on feed intake, digestive processes, and performance of mid-lactation Holstein cows

The aim of this study was to evaluate effects of partial replacement of neutral detergent soluble fibre (NDSF) for starch in diets varying in particle size (PS) of alfalfa hay on chewing activities, ruminal fermentation, nutrient digestibility and performance in mid-lactation dairy cows. Eight multiparous Holstein cows (146 ± 6.0 d in milk; 36.7 ± 2.57 kg milk/d) were used in a replicated 4 × 4 Latin square design with four 21 d periods with the last 7 d for data collection. The experiment was a 2 × 2 factorial arrangement with 2 levels of NDSF (low = 85 g/kg or high = 130 g/kg diet dry matter) each combined with 2 PS (short = 20 mm or long = 40 mm) of alfalfa hay. Results show that forage PS alone, or in combination with NDSF inclusion, had no effect on dry matter (DM) intake. Although total chewing, eating and ruminating times were not affected by treatments, eating time per kg of neutral detergent fibre (NDF) ingested was higher in long versus short alfalfa hay-based diets (P<0.05). Feeding long forage PS increased sorting of the diet against particles >19 mm, and in favor of those <8 mm (P<0.05). Feeding diets high in NDSF lowered DM intake (P<0.05), but increased apparent digestibility of all nutrients including NDF (P<0.05) independent of forage PS. Ruminal pH and concentrations of total volatile fatty acids were unaffected by dietary treatments, however the proportion of butyrate was higher in ruminal fluid of cows fed high NDSF diets (P<0.05). Changes in milk composition included lower milk crude protein content in high NDSF diets and higher lactose content for short hay-based diets (P<0.05). That milk yield and milk energy output were similar in low versus high NDSF diets suggests that high NDSF-fed cows had higher energy efficiency due to lower DM intake. Results suggest that, independent of forage PS, NDSF sources can be successfully included to partly replace starchy grains in diets exceeding minimum fibre recommendations.     

Spatial Mapping of the Biomechanical Properties of the Pericellular Matrix of Articular Cartilage Measured In Situ via Atomic Force Microscopy

In articular cartilage, chondrocytes are surrounded by a narrow region called the pericellular matrix (PCM), which is biochemically, structurally, and mechanically distinct from the bulk extracellular matrix (ECM). Although multiple techniques have been used to measure the mechanical properties of the PCM using isolated chondrons (the PCM with enclosed cells), few studies have measured the biomechanical properties of the PCM in situ. The objective of this study was to quantify the in situ mechanical properties of the PCM and ECM of human, porcine, and murine articular cartilage using atomic force microscopy (AFM). Microscale elastic moduli were quantitatively measured for a region of interest using stiffness mapping, or force-volume mapping, via AFM. This technique was first validated by means of elastomeric models (polyacrylamide or polydimethylsiloxane) of a soft inclusion surrounded by a stiff medium. The elastic properties of the PCM were evaluated for regions surrounding cell voids in the middle/deep zone of sectioned articular cartilage samples. ECM elastic properties were evaluated in regions visually devoid of PCM. Stiffness mapping successfully depicted the spatial arrangement of moduli in both model and cartilage surfaces. The modulus of the PCM was significantly lower than that of the ECM in human, porcine, and murine articular cartilage, with a ratio of PCM to ECM properties of ∼0.35 for all species. These findings are consistent with previous studies of mechanically isolated chondrons, and suggest that stiffness mapping via AFM can provide a means of determining microscale inhomogeneities in the mechanical properties of articular cartilage in situ.     

An overview of Iranian mangrove ecosystems, northern part of the Persian Gulf and Oman Sea

Iranian mangrove forests occur between longitude 25°19′ and 27°84′, in the north part of the Persian Gulf and Oman Sea. In 2002, it was estimated that 93.37 km² of Iranian shorelines were covered with mangrove forests, with the largest area (67.5 km²) occurring between the Khamir Port and the northwest side of Qeshm Island, and the smallest area (0.01 km²) in the Bardestan estuary. Only two species of mangrove are found in the Persian Gulf: Avicennia marina from Avicenniaceae and Rhizophora macrunata from Rhizophoraceae. A. marina is the dominant specie in these forests whereas Rh. macrunata is found only in the Sirik region. Overexploitation of mangrove leaves and oil pollution are the main causes of mangrove destruction in this region.     

Highly efficient and selective methoxymethylation of alcohols and phenols catalyzed by high-valent tin(IV) porphyrin

An efficient and selective method for methoxymethylation of alcohols and phenols with formaldehyde dimethyl acetal (FDMA) catalyzed by electron deficient tin(IV)tetraphenylporphyrinato trifluoromethanesulfonate, [Sn^IV(TPP)(OTf)₂], is reported. A variety of primary, secondary and tertiary alcohols as well as phenols were converted to their corresponding methoxymethyl ethers with FDMA in the presence of a high-valent tin(IV) porphyrin. This catalyst can be used for selective methoxymethylation of primary, secondary and tertiary alcohols in the presence of phenols or tertiary alcohols. The present method offers several advantages such as short reaction times, high yields, simple procedure, selectivity and applicability for both alcohols and phenols.     

Effects of the litter layer of Pteridium aquilinum on seed banks under experimental restoration

Questions: Does the litter layer of Pteridium aquilinum (bracken) act as a barrier to certain species in the seed bank? Does bracken control/restoration treatment affect seed transfer through the litter layer? Location: Five experiments at three sites across the UK covering two major vegetation types; acid‐grassland and heath‐land. Methods: At each experiment a range of bracken control and vegetation restoration treatments were applied for about ten years. The seed bank was sampled in both the bracken litter and the soil. The cover (%) of each species in the vegetation and the bracken litter abundance (cover and depth) was also estimated. Results: The bracken litter layer acts as an inert barrier as it contained a large proportion of seeds available in the litter‐soil profile (38%– 67% of the total). Bracken litter depth and cover also influenced significantly the seed bank composition in both the bracken litter and the soil. These effects were site‐specific, and species‐specific. The application of treatments changed significantly the balance between seed inputs and outputs in the bracken litter layer for some species. This was either a positive or negative response relative to the untreated control plots. Conclusion: For heathland and acid‐grassland restoration, the bracken litter layer may be an important seed source, but it must be disturbed particularly before seed addition.