Genetic associations with temporal shifts in obesity and severe obesity during the obesity epidemic in Norway:A longitudinal population-based cohort (the HUNT Study)

Background Obesity has tripled worldwide since 1975 as environments are becoming more obesogenic. Our study investigates how changes in population weight and obesity over time are associated with genetic predisposition in the context of an obesogenic environment over 6 decades and examines the robustness of the findings using sibling design. Methods and findings A total of 67,110 individuals aged 13–80 years in the Nord-Trøndelag region of Norway participated with repeated standardized body mass index (BMI) measurements from 1966 to 2019 and were genotyped in a longitudinal population-based health study, the Trøndelag Health Study (the HUNT Study). Genotyping required survival to and participation in the HUNT Study in the 1990s or 2000s. Linear mixed models with observations nested within individuals were used to model the association between a genome-wide polygenic score (GPS) for BMI and BMI, while generalized estimating equations were used for obesity (BMI ≥ 30 kg/m2) and severe obesity (BMI ≥ 35 kg/m2). The increase in the average BMI and prevalence of obesity was steeper among the genetically predisposed. Among 35-year-old men, the prevalence of obesity for the least predisposed tenth increased from 0.9% (95% confidence interval [CI] 0.6% to 1.2%) to 6.5% (95% CI 5.0% to 8.0%), while the most predisposed tenth increased from 14.2% (95% CI 12.6% to 15.7%) to 39.6% (95% CI 36.1% to 43.0%). Equivalently for women of the same age, the prevalence of obesity for the least predisposed tenth increased from 1.1% (95% CI 0.7% to1.5%) to 7.6% (95% CI 6.0% to 9.2%), while the most predisposed tenth increased from 15.4% (95% CI 13.7% to 17.2%) to 42.0% (95% CI 38.7% to 45.4%). Thus, for 35-year-old men and women, respectively, the absolute change in the prevalence of obesity from 1966 to 2019 was 19.8 percentage points (95% CI 16.2 to 23.5, p < 0.0001) and 20.0 percentage points (95% CI 16.4 to 23.7, p < 0.0001) greater for the most predisposed tenth compared with the least predisposed tenth, defined using the GPS for BMI. The corresponding absolute changes in the prevalence of severe obesity for men and women, respectively, were 8.5 percentage points (95% CI 6.3 to 10.7, p < 0.0001) and 12.6 percentage points (95% CI 9.6 to 15.6, p < 0.0001) greater for the most predisposed tenth. The greater increase in BMI in genetically predisposed individuals over time was apparent after adjustment for family-level confounding using a sibling design. Key limitations include a slightly lower survival to date of genetic testing for the older cohorts and that we apply a contemporary genetic score to past time periods. Future research should validate our findings using a polygenic risk score constructed from historical data. Conclusions In the context of increasingly obesogenic changes in our environment over 6 decades, our findings reveal a growing inequality in the risk for obesity and severe obesity across GPS tenths. Our results suggest that while obesity is a partially heritable trait, it is still modifiable by environmental factors. While it may be possible to identify those most susceptible to environmental change, who thus have the most to gain from preventive measures, efforts to reverse the obesogenic environment will benefit the whole population and help resolve the obesity epidemic

Considering the food environment can help to promote the consumption of aquatic foods for healthy diets

Aquatic foods ensure food and nutrition security for billions of consumers around the world. As part of food systems, aquatic foods provide nutritious, affordable, convenient options for healthy diets, and can also foster sustainable food production. Within the food system framework, the food environment is the space that connects food procurement to consumption. The food environment influences consumer decisions on which foods to acquire. To date there has been relatively little focus on creating an enabling food environment that supports consumers in decisions to obtain aquatic foods. To fill this gap, we conducted a narrative review of literature from 2000–2020 to document the availability, affordability, convenience, promotion, quality and sustainability of aquatic foods within diverse food environments. Our review highlighted several opportunities that can support development and promotion of convenient, high quality aquatic foods. We also noted several research gaps. For example, some consumers, especially those in high income countries, respond well to labels related to sustainability and also to messaging to consume diverse types of fish, especially lower tropic species like anchovy. However, less is documented on how promotion influences consumers from LMIC. The paper also notes a gap in assessment of the price and affordability of aquatic foods. Most price and affordability assessments do not provide details on which aquatic foods were considered in the costing assessment. In addition, wild or home-harvested aquatic foods are often not accounted for in price and affordability assessments. Using case studies, we demonstrate how considering the food environment in research and implementation strategies can add value to program design. For example, processing tuna frames and underutilized small fish species into powder is one innovation that reduces food waste and also creates a convenient, quality product. These results provide the foundation for deepening our understanding of how key elements of the food environment influence consumers’ decision-making and how these elements can be considered in future research, programming and policy efforts

Congenital dislocation of the hip: Optimal screening strategies in 2014

AbstractA prospective multi-centre nationwide study of patients with congenital dislocation of the hip (CDH) diagnosed after 3 months of age was conducted with support from the French Society for Paediatric Orthopaedics (Société Française d’Orthopédie Pédiatrique [SoFOP]), French Organisation for Outpatient Paediatrics (Association Française de Pédiatrie Ambulatoire [AFPA]), and French-Speaking Society for Paediatric and Pre-Natal Imaging (Société Francophone d’Imagerie Pédiatrique et Prénatale [SFIPP]). The results showed inadequacies in clinical screening for CDH that were patent when assessed quantitatively and probably also present qualitatively. These findings indicate a need for a communication and educational campaign aimed at highlighting good clinical practice guidelines in the field of CDH screening. The usefulness of routine ultrasound screening has not been established. The findings from this study have been used by the authors and French National Health Authority (Haute Autorité de Santé [HAS]) to develop recommendations about CDH screening. There is an urgent need for a prospective randomised multi-centre nationwide study, which should involve primary-care physicians

Vitamin E and selenium plasma concentrations in weanling pigs under field conditions in Norwegian pig herds

BACKGROUND: The status of α-tocopherol (vit E) and selenium (Se) has been shown to influence disease resistance in pigs, and may be important for the health of weanling pigs. METHODS: Plasma levels of both vit E and Se were followed in weanling pigs under field conditions in six Norwegian pig herds. Plasma vit E and Se were measured in 3 sows from each herd and 4 piglets in the litter of each sow at the day before weaning (day -1); and in the same piglets at days 4, 8 and 18 after weaning. RESULTS: Mean plasma vit E was 4.0 μg/ml in the sows and 2.6 μg/ml in the piglets at day -1, fell to 1.6 μg/ml in the weanling pigs at day 4, and remained low. Mean plasma Se was 0.22 μg/g in the sows and 0.08 μg/g in the piglets at day -1, rose to 0.10 μg/g in the weanlings at day 4, and continued rising. CONCLUSION: The results suggest that vit E and Se supplementation to piglets and weanling pigs in Norway may still be suboptimal, but that levels of the two nutrients partially compensate for each other in the weaning period

Evidence of a causal relationship between body mass index and psoriasis:A mendelian randomization study

Background: Psoriasis is a common inflammatory skin disease that has been reported to be associated with obesity. We aimed to investigate a possible causal relationship between body mass index (BMI) and psoriasis. Methods and Findings: Following a review of published epidemiological evidence of the association between obesity and psoriasis, mendelian randomization (MR) was used to test for a causal relationship with BMI. We used a genetic instrument comprising 97 single-nucleotide polymorphisms (SNPs) associated with BMI as a proxy for BMI (expected to be much less confounded than measured BMI). One-sample MR was conducted using individual-level data (396,495 individuals) from the UK Biobank and the Nord-Trøndelag Health Study (HUNT), Norway. Two-sample MR was performed with summary-level data (356,926 individuals) from published BMI and psoriasis genome-wide association studies (GWASs). The one-sample and two-sample MR estimates were meta-analysed using a fixed-effect model. To test for a potential reverse causal effect, MR analysis with genetic instruments comprising variants from recent genome-wide analyses for psoriasis were used to test whether genetic risk for this skin disease has a causal effect on BMI. Published observational data showed an association of higher BMI with psoriasis. A mean difference in BMI of 1.26 kg/m2 (95% CI 1.02-1.51) between psoriasis cases and controls was observed in adults, while a 1.55 kg/m2 mean difference (95% CI 1.13-1.98) was observed in children. The observational association was confirmed in UK Biobank and HUNT data sets. Overall, a 1 kg/m2 increase in BMI was associated with 4% higher odds of psoriasis (meta-analysis odds ratio [OR] = 1.04; 95% CI 1.03-1.04; P = 1.73 × 10-60). MR analyses provided evidence that higher BMI causally increases the odds of psoriasis (by 9% per 1 unit increase in BMI; OR = 1.09 (1.06-1.12) per 1 kg/m2; P = 4.67 × 10-9). In contrast, MR estimates gave little support to a possible causal effect of psoriasis genetic risk on BMI (0.004 kg/m2 change in BMI per doubling odds of psoriasis (-0.003 to 0.011). Limitations of our study include possible misreporting of psoriasis by patients, as well as potential misdiagnosis by clinicians. In addition, there is also limited ethnic variation in the cohorts studied. Conclusions: Our study, using genetic variants as instrumental variables for BMI, provides evidence that higher BMI leads to a higher risk of psoriasis. This supports the prioritization of therapies and lifestyle interventions aimed at controlling weight for the prevention or treatment of this common skin disease. Mechanistic studies are required to improve understanding of this relationship

The direct effect of Focal Adhesion Kinase (FAK), dominant-negative FAK, FAK-CD and FAK siRNA on gene expression and human MCF-7 breast cancer cell tumorigenesis

<p>Abstract</p> <p>Background</p> <p>Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that plays an important role in survival signaling. FAK has been shown to be overexpressed in breast cancer tumors at early stages of tumorigenesis.</p> <p>Methods</p> <p>To study the direct effect of FAK on breast tumorigenesis, we developed Tet-ON (tetracycline-inducible) system of MCF-7 breast cancer cells stably transfected with FAK or dominant-negative, C-terminal domain of FAK (FAK-CD), and also FAKsiRNA with silenced FAK MCF-7 stable cell line. Increased expression of FAK in isogenic Tet-inducible MCF-7 cells caused increased cell growth, adhesion and soft agar colony formation <it>in vitro</it>, while expression of dominant-negative FAK inhibitor caused inhibition of these cellular processes. To study the role of induced FAK and FAK-CD <it>in vivo</it>, we inoculated these Tet-inducible cells in nude mice to generate tumors in the presence or absence of doxycycline in the drinking water. FAKsiRNA-MCF-7 cells were also injected into nude mice to generate xenograft tumors.</p> <p>Results</p> <p>Induction of FAK resulted in significant increased tumorigenesis, while induced FAK-CD resulted in decreased tumorigenesis. Taq Man Low Density Array assay demonstrated specific induction of FAKmRNA in MCF-7-Tet-ON-FAK cells. DMP1, encoding cyclin D binding myb-like protein 1 was one of the genes specifically affected by Tet-inducible FAK or FAK-CD in breast xenograft tumors. In addition, silencing of FAK in MCF-7 cells with FAK siRNA caused increased cell rounding, decreased cell viability <it>in vitro </it>and inhibited tumorigenesis <it>in vivo</it>. Importantly, Affymetrix microarray gene profiling analysis using Human Genome U133A GeneChips revealed >4300 genes, known to be involved in apoptosis, cell cycle, and adhesion that were significantly down- or up-regulated (p < 0.05) by FAKsiRNA.</p> <p>Conclusion</p> <p>Thus, these data for the first time demonstrate the direct effect of FAK expression and function on MCF-7 breast cancer tumorigenesis <it>in vivo </it>and reveal specific expression of genes affected by silencing of FAK.</p