Consumption of Common Bean Suppresses the Obesogenic Increase in Adipose Depot Mass: Impact of Dose and Biological Sex.

Obesity prevention is stated as a simple objective in the public health guidelines of most countries: avoid adult weight gain. However, the success of the global population in accomplishing this goal is limited as reflected in the persisting pandemic of overweight and obesity. While many intervention strategies have been proposed, most are directed at mitigating the consequences of obesity. Efforts intended to prevent unintentional weight gain and associated adiposity are termed anti-obesogenic. Herein, evidence is presented that a neglected category of foods, pulses, i.e., grain legumes, have anti-obesogenic activity. Using a preclinical mouse model of obesity, a dose-response study design in animals of both biological sexes, and cooked, freeze-dried, and milled common bean as a representative pulse, data are presented showing that the rate of body weight gain is slowed, and fat accumulation is suppressed when 70% of the dietary protein is provided from common bean. These anti-obesogenic effects are reduced at lower amounts of common bean (17.5% or 35%). The anti-obesogenic responsiveness is greater in female than in male mice. RNA sequence analysis indicates that the sex-related differences extend to gene expression patterns, particularly those related to immune regulation within adipose tissue. In addition, our findings indicate the potential value of a precision nutrition approach for human intervention studies that identify "pulse anti-obesogenic responders". A precision approach may reduce the concentration of pulses required in the diet for benefits, but candidate biomarkers of responsivity to pulse consumption remain to be determined.

"I am not a number!" Opinions and preferences of people with intellectual disability about genetic healthcare.

There is limited research exploring the knowledge and experiences of genetic healthcare from the perspective of people with intellectual disability. This study, conducted in New South Wales (Australia), addresses this gap. Eighteen adults with intellectual disability and eight support people were interviewed in this inclusive research study. The transcribed interviews were analysed using inductive content analysis. The findings were discussed in a focus group with ten adults with intellectual disability and in three multi-stakeholder advisory workshops, contributing to the validity and trustworthiness of the findings. Five main themes emerged: (i) access to genetic healthcare services is inequitable, with several barriers to the informed consent process; (ii) the experiences and opinions of people with intellectual disability are variable, including frustration, exclusion and fear; (iii) genetic counselling and diagnoses can be profoundly impactful, but translating a genetic diagnosis into tailored healthcare, appropriate support, peer connections and reproductive planning faces barriers; (iv) people with intellectual disability have a high incidence of exposure to trauma and some reported that their genetic healthcare experiences were associated with further trauma; (v) recommendations for a more respectful and inclusive model of genetic healthcare. Co-designed point-of-care educational and consent resources, accompanied by tailored professional education for healthcare providers, are required to improve the equity and appropriateness of genetic healthcare for people with intellectual disability.

A Randomized, Double-Blind, Placebo-Controlled Investigation of Selenium Supplementation in Women at Elevated Risk for Breast Cancer: Lessons for Re-Emergent Interest in Selenium and Cancer.

Damage to cellular macromolecules such as DNA and lipid, induced via reactive oxygen species, and indicators of cell proliferation potential such as insulin-like growth factor (IGF) metabolic status are intermediate biomarkers of breast cancer risk. Based on reports that selenium status can affect these markers, a randomized, placebo-controlled, double-blind experiment was conducted to investigate the potential of selenium supplementation to modulate breast cancer risk. Using a placebo tablet or a tablet containing 200 µg selenium provided as high-selenium yeast daily for one year, concentrations of the biomarkers in blood or urine were assessed at baseline and after 6 and 12 months of intervention. The selenium intervention used in this study is presumed to mediate its effect via the induction of glutathione peroxidase activity and the consequential impact of the active form of this protein on oxidative damage. We found no evidence to support this hypothesis or to indicate that systemic IGF metabolic status was affected. Critical knowledge gaps must be addressed for the resurgence of interest in selenium and cancer to garner clinical relevance. Those knowledge gaps include the identification of a specific, high-affinity selenium metabolite and the cellular target(s) to which it binds, and the demonstration that the cellular determinant that the selenium metabolite binds plays a critical role in the initiation, promotion, or progression of a specific type of cancer.

Paediatric genomic testing: Navigating medicare rebatable genomic testing.

Genomic testing for a genetic diagnosis is becoming standard of care for many children, especially those with a syndromal intellectual disability. While previously this type of specialised testing was performed mainly by clinical genetics teams, it is increasingly being 'mainstreamed' into standard paediatric care. With the introduction of a new Medicare rebate for genomic testing in May 2020, this type of testing is now available for paediatricians to order, in consultation with clinical genetics. Children must be aged less than 10 years with facial dysmorphism and multiple congenital abnormalities or have global developmental delay or moderate to severe intellectual disability. This rebate should increase the likelihood of a genetic diagnosis, with accompanying benefits for patient management, reproductive planning and diagnostic certainty. Similar to the introduction of chromosomal microarray into mainstream paediatrics, this genomic testing will increase the number of genetic diagnoses, however, will also yield more variants of uncertain significance, incidental findings, and negative results. This paper aims to guide paediatricians through the process of genomic testing, and represents the combined expertise of educators, clinical geneticists, paediatricians and genomic pathologists around Australia. Its purpose is to help paediatricians navigate choosing the right genomic test, consenting patients and understanding the possible outcomes of testing.

Building a Foundation for Precision Onco-Nutrition: Docosahexaenoic Acid and Breast Cancer.

In vivo evidence of heterogeneous effects of n-3 fatty acids (N3FA) on cell signaling pathways associated with the reduced growth of breast cancer has been reported and is consistent with the expectation that N3FA will not exert uniform effects on all molecular subtypes of the disease. Similarly, available evidence indicates that many metabolites of N3FA are synthesized by mammalian cells and that they exert metabolite-specific biological activities. To begin to unravel the complex relationships among molecular subtypes and effects exerted by specific N3FA metabolites on those pathways, proof-of-concept experiments were conducted using cell lines representative of common molecular subtypes of human breast cancer. N3FA differed in anticancer activity with docosahexaenoic acid (DHA) having greater anticancer activity than eicosapentaenoic acid. 4-oxo-docosahexaenoic (4-oxo-DHA), a penultimate metabolite of 5-lipoxygenase mediated DHA metabolism, induced dose-dependent inhibition of cell number accumulation with apoptosis as a primary effector mechanism. Interrogation of protein expression data using the Ingenuity Pathway Analysis (IPA) bioinformatics platform indicated that 4-oxo-DHA differentially impacted six canonical pathways and the cellular functions they regulate across common molecular subtypes of breast cancer. This included the endocannabinoid pathway for cancer inhibition that has not been previously reported. These findings provide a rationale for juxtaposing molecular subtype targeted treatment strategies with the adjuvant use of specific N3FA metabolites as an example of precision onco-nutrition (PON) for the management and control of breast cancer.

Pulse Crop Effects on Gut Microbial Populations, Intestinal Function, and Adiposity in a Mouse Model of Diet-Induced Obesity.

The dietary fiber gap that is present in many countries co-exists with a low intake of grain legumes (pulses) that have 2-3 times more dietary fiber than cereal grains that are commonly recommended to increase fiber intake. Given the relationships among dietary fiber, gut health and chronic disease risk, a study was undertaken in a preclinical mouse model for obesity to examine how commonly consumed pulses, i.e., chickpea, common bean, dry pea and lentil, would impact gut microbes, intestinal function, and adiposity. Pulses were fed to C57BL/6 mice at similar levels of protein and fiber. Bacterial count in the cecum was elevated 3-fold by pulse consumption. At the phylum level, a 2.2- to 5-fold increase in Bacteriodetes relative to Firmicutes was observed. For Akkermansia muciniphila, a health-beneficial bacterium, differential effects were detected among pulses ranging from no effect to a 49-fold increase. Significant differences among pulses in biomarkers of intestinal function were not observed. Pulses reduced accumulation of lipid in adipose tissue with a greater reduction in the subcutaneous versus visceral depots. Metabolomics analysis indicated that 108 metabolites were highly different among pulse types, and several compounds are hypothesized to influence the microbiome. These results support recent recommendations to increase consumption of pulse-based foods for improved health, although all pulses were not equal in their effects.

White Kidney Bean (Phaseolus Vulgaris L.) Consumption Reduces Fat Accumulation in a Polygenic Mouse Model of Obesity.

Clinical studies indicate that eating common bean, Phaseolus vulgaris L., plays a role in body weight regulation but mechanisms have yet to be elucidated. Here, we investigated the anti-obesogenic activity of white kidney bean in a mouse model of dietary-induced obesity. Bean consumption reduced the accumulation of adipose tissue in male and female C57BL6 mice. The anti-obesogenic effect of white kidney bean was not due to alterations in energy intake, energy excreted in the feces, or feed efficiency ratio. While bean consumption increased the mass of the intestine, no marked differences were consistently observed in crypt height, mucin content of goblet cells, proliferation index or zone of proliferation. However, significantly higher concentrations of total bacteria and of Akkermansia muciniphila were detected in cecal content of bean-fed mice, and the ratio of Firmicutes to Bacteroidetes was reduced. Bile acid content was higher in the ileum of bean-fed mice, but transcript levels of farnesoid X receptor were not significantly affected. Whether changes in bile-acid-mediated cell signaling play a role in bean-related differences in fat accumulation and/or overall metabolic health requires further investigation.

Evaluation of diversity among common beans (Phaseolus vulgaris L.) from two centers of domestication using 'omics' technologies.

BACKGROUND: Genetic diversity among wild accessions and cultivars of common bean (Phaseolus vulgaris L.) has been characterized using plant morphology, seed protein allozymes, random amplified polymorphic DNA, restriction fragment length polymorphisms, DNA sequence analysis, chloroplast DNA, and microsatellite markers. Yet, little is known about whether these traits, which distinguish among genetically distinct types of common bean, can be evaluated using omics technologies. RESULTS: Three 'omics' approaches: transcriptomics, proteomics, and metabolomics were used to qualitatively evaluate the diversity of common bean from two Centers of Domestication (COD). All three approaches were able to classify common bean according to their COD using unsupervised analyses; these findings are consistent with the hypothesis that differences exist in gene transcription, protein expression, and synthesis and metabolism of small molecules among common bean cultivars representative of different COD. Metabolomic analyses of multiple cultivars within two common bean gene pools revealed cultivar differences in small molecules that were of sufficient magnitude to allow identification of unique cultivar fingerprints. CONCLUSIONS: Given the high-throughput and low cost of each of these 'omics' platforms, significant opportunities exist for their use in the rapid identification of traits of agronomic and nutritional importance as well as to characterize genetic diversity.

Characterization of low molecular weight chemical fractions of dry bean (Phaseolus vulgaris) for bioactivity using Caenorhabditis elegans longevity and metabolite fingerprinting.

Dry bean consumption has been reported to be associated with reduced risk for a number of chronic diseases including cancer. The extent to which these benefits are associated with primary versus secondary plant metabolites is not known. The work reported herein focuses on low molecular weight secondary metabolites and uses longevity extension of wild-type Caenorhabditis elegans nematodes as a surrogate marker for human health benefits. A modified Bligh and Dyer technique was used to extract freeze-dried bean, and the resulting fractions were evaluated for longevity extension and metabolite fingerprinting using ultra performance liquid chromatography-mass spectrometry (UPLC-MS). Dry bean extracts extended adult C. elegans lifespan by as much as 16%. Hydrophilic fractions increased lifespan, whereas the hydrophobic fraction induced longevity reduction. Metabolite fingerprinting revealed distinguishing spectral differences among the four chemical fractions evaluated and demonstrated that within each fraction chemical composition differed significantly based on dry bean genetic heritage.

A transfer-less, multi-well liquid culture feeding system for screening small molecules that affect the longevity of Caenorhabditis elegans.

Agricultural sciences rely almost entirely on chemical assays to screen the thousands of crop cultivars generated in a crop improvement program for potential human health benefits. This situation exists in part because most animal models are expensive to implement, utilize large amounts of plant material, and require specialized facilities and technical training. A cost-effective, high-throughput animal model to screen crop extracts for small molecules with biological activity related to human health benefits would provide a much-needed resource. Here we introduce a new, relatively high-throughput method incorporating the microscopic Caenorhabditis elegans nematode, which is suitable for screening chemical extracts for bioactivity without the need for robotics. This system was chosen because longevity extension in C. elegans has been previously associated with human health benefits. Through the use of cell culture inserts, C. elegans can be exposed to fresh crop extracts daily throughout their lifespan without mechanical manipulation of the worm, thus minimizing stress and creating an environment suitable for experiments measuring longevity. Additionally, the duration of longevity experiments can be reduced by using type II right censoring in experimental design and survival analyses.