Environmental components of childhood obesity prevention interventions: an overview of systematic reviews.

Childhood obesity has a complex multi-factorial aetiology grounded in environmental and individual level factors that affect behaviour and outcomes. An ecological, systems-based approach to addressing childhood obesity is increasingly being advocated. The primary aim of this review is to summarize the evidence reported in systematic reviews on the effectiveness of population-level childhood obesity prevention interventions that have an environmental component. We conducted a systematic review of reviews published since 1995, employing a standardized search strategy in nine databases. Inclusion criteria required that reviews be systematic and evaluated at least one population-level, environmental intervention in any setting aimed at preventing or reducing obesity in children (5-18 years). Sixty-three reviews were included, ten of which were of high quality. Results show modest impact of a broad range of environmental strategies on anthropometric outcomes. Systematic reviews vary in methodological quality, and not all relevant primary studies may be included in each review. To ensure relevance of our findings to practice, we also report on relevant underlying primary studies, providing policy-relevant recommendations based on the evidence reviewed. Greater standardization of review methods and reporting structures will benefit policymakers and public health professionals seeking informed decision-making

Common variants of the TCF7L2 gene are associated with increased risk of type 2 diabetes mellitus in a UK-resident South Asian population

Background Recent studies have implicated variants of the transcription factor 7-like 2 (TCF7L2) gene in genetic susceptibility to type 2 diabetes mellitus in several different populations. The aim of this study was to determine whether variants of this gene are also risk factors for type 2 diabetes development in a UK-resident South Asian cohort of Punjabi ancestry. Methods We genotyped four single nucleotide polymorphisms (SNPs) of TCF7L2 (rs7901695, rs7903146, rs11196205 and rs12255372) in 831 subjects with diabetes and 437 control subjects. Results The minor allele of each variant was significantly associated with type 2 diabetes; the greatest risk of developing the disease was conferred by rs7903146, with an allelic odds ratio (OR) of 1.31 (95% CI: 1.11 – 1.56, p = 1.96 × 10-3). For each variant, disease risk associated with homozygosity for the minor allele was greater than that for heterozygotes, with the exception of rs12255372. To determine the effect on the observed associations of including young control subjects in our data set, we reanalysed the data using subsets of the control group defined by different minimum age thresholds. Increasing the minimum age of our control subjects resulted in a corresponding increase in OR for all variants of the gene (p ≤ 1.04 × 10-7). Conclusion Our results support recent findings that TCF7L2 is an important genetic risk factor for the development of type 2 diabetes in multiple ethnic groups

TCF7L2 rs7903146-macronutrient interaction in obese individuals' responses to a 10-wk randomized hypoenergetic diet

BACKGROUND: Transcription factor 7-like 2 (TCF7L2) rs7903146 associates with type 2 diabetes and may operate via impaired glucagon-like peptide 1 secretion, which is stimulated more by fat than by carbohydrate ingestion. OBJECTIVE: The objective was to examine the interaction between TCF7L2 rs7903146 and dietary fat and carbohydrate [high-fat, low-carbohydrate: 40-45% of energy as fat (HF); compared with low-fat, high-carbohydrate: 20-25% of energy as fat (LF)] in obese individuals' responses to a 10-wk hypoenergetic diet (-600 kcal/d). DESIGN: European, obese participants (n = 771) were randomly assigned to receive an HF or an LF diet. Body weight, fat mass (FM), fat-free mass (FFM), waist circumference (WC), resting energy expenditure (REE), fasting fat oxidation in percentage of REE (FatOx), homeostasis model assessed insulin release (HOMA-beta), and HOMA-insulin resistance (HOMA-IR) were determined at baseline and after the intervention; 739 individuals were genotyped for rs7903146. RESULTS: Average weight loss was 6.9 kg with the LF and 6.6 kg with the HF (difference between diets, NS) diet. Among individuals who were homozygous for the T-risk allele, those in the HF diet group experienced smaller weight losses (Deltaweight) (2.6 kg; P = 0.009; n = 622), smaller DeltaFFM (1.6 kg; P = 0.027; n = 609), smaller DeltaWC (3.3 cm; P = 0.010; n = 608), and a smaller DeltaHOMA-IR (1.3 units; P = 0.004; n = 615) than did the LF diet group. For C allele carriers, there were no differences between the HF and LF diet groups. For the HF diet group, each additional T allele was associated with a reduced loss of FM (0.67 kg; P = 0.019; n = 609). TCF7L2 rs7903146 was not associated with DeltaREE, DeltaFatOx, DeltaHOMA-beta, or dropout. CONCLUSION: Our results suggest that obese individuals who are homozygous for the TCF7L2 rs7903146 T-risk allele are more sensitive to LF than to HF weight-loss diets

Childhood obesity in Malta: contributions of the obesogenic environment.

Background. There is a high prevalence of childhood obesity in Malta. The aim of this research is to gain insight into the environmental drivers of childhood obesity in Malta, and identify opportunities for an environmental approach to obesity prevention. Methods. This thesis comprises: (i) a contextual analysis of childhood obesity and the policy response in Malta; (ii) an overview of systematic reviews to identify environmental components of effective prevention interventions; (iii) an assessment of Maltese television advertising; (iv) an environmental audit of the food and built environment; (v) semi-structured interviews and focus groups with key informants; and (vi) microsimulation modelling to forecast the future health and economic burden of obesity in Malta. Results. Numerous environmental factors at multiple levels deter healthy dietary and physical activity behaviour among Maltese children. These include an obesogenic built environment that provides few opportunities for play or active transport, and a food environment characterised by easy access to, and heavy promotion of, energy-dense foods and beverages. The contextual analysis and environmental audit revealed several obesogenic aspects of the environment in Malta, such as substantial promotion of food high in fat, sugar and salt to children on local TV channels and a price premium for certain healthy food options in grocery stores. Thematic analysis of qualitative data revealed numerous barriers to healthy behaviours for Maltese children, including parental concerns about traffic hazard leading to restricted physical activity, and familal dietary patterns which encourage over-consumption of food. Interviews with food industry and public health actors also highlighted ‘framings’ of obesity that closely matched those described in the international literature. Microsimulation modelling illustrated the substantial financial savings and reductions in noncommunicable disease incidence if population weight reduction were to be achieved. Conclusions. An obesogenic environment underlies the problem of childhood obesity in Malta. The socio-ecological approach used in this research highlighted key areas for intervention and illustrated the importance of taking context into account when designing national obesity-prevention efforts

Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility.

To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry

Self-oligomerization regulates stability of survival motor neuron protein isoforms by sequestering an SCF^Slmb degron

Spinal muscular atrophy (SMA) is caused by homozygous mutations in human SMN1. Expression of a duplicate gene (SMN2) primarily results in skipping of exon 7 and production of an unstable protein isoform, SMNΔ7. Although SMN2 exon skipping is the principal contributor to SMA severity, mechanisms governing stability of survival motor neuron (SMN) isoforms are poorly understood. We used a Drosophila model system and label-free proteomics to identify the SCFSlmb ubiquitin E3 ligase complex as a novel SMN binding partner. SCFSlmb interacts with a phosphor degron embedded within the human and fruitfly SMN YG-box oligomerization domains. Substitution of a conserved serine (S270A) interferes with SCFSlmb binding and stabilizes SMNΔ7. SMA-causing missense mutations that block multimerization of full-length SMN are also stabilized in the degron mutant background. Overexpression of SMNΔ7S270A, but not wild-type (WT) SMNΔ7, provides a protective effect in SMA model mice and human motor neuron cell culture systems. Our findings support a model wherein the degron is exposed when SMN is monomeric and sequestered when SMN forms higher-order multimers

Regional varieties of \u27left-behindness\u27 in the EU15

\ua9 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. Recent debates about ‘left behind’ places have opened up new opportunities to understand the interconnected challenges faced by many regions in the Global North. At the same time, the application of this label to a wide variety of places with different characteristics has been accused of obscuring as much as it reveals. In this paper, we shed light on the variegated nature of ‘left behind’ regions through a cluster analysis of NUTS-3 regions in the EU15. We identify six types of areas, of which three are characterised as ‘left behind’ based on their performance on a range of economic, demographic and social variables. There are important differences between these three types of regions, strengthening the argument for policy responses adapted to local circumstances