ArticlePLoS genetics2021
Genes in human obesity loci are causal obesity genes in C. elegans.
Article in PLoS genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 31 citations in OpenAlex.
- Evaluating the Validity of Model Organisms: A Review and a New Framework for Biologists.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
- A conserved C. elegans zinc finger homeodomain protein, ZFH-2, is continuously required for the structural integrity and function of the alimentary tract and gonad.Development (Cambridge, England) · 2026Article
- A conservedbioRxiv : the preprint server for biology · 2026Article
- Conserved NT5C2 links context-specific behaviors with psychiatric and metabolic risk.Behavioral and brain functions : BBF · 2026Article
- Proximity labeling of DAF-16 FOXO highlights aging regulatory proteins.Nature communications · 2025Article
- Anti-obesity peptides from food: Production, evaluation, sources, and commercialization.Comprehensive reviews in food science and food safety · 2025Review
- Evaluation of Potential Roles of Zinc Finger Homeobox 3 (Zfhx3) Expressed in Chondrocytes and Osteoblasts on Skeletal Growth in Mice.Calcified tissue international · 2024Article
- Inferring causal direction between two traits using RAmerican journal of human genetics · 2024Article
- Fast and Accurate Estimation of Selection Coefficients and Allele Histories from Ancient and Modern DNA.Molecular biology and evolution · 2024Article
- Dietary supplementation with probiotics promotes weight loss by reshaping the gut microbiome and energy metabolism in obese dogs.Microbiology spectrum · 2024Article
- Case report: An adolescent female with anosmic hypogonadotropic hypogonadism, intellectual disability, and papillary thyroid carcinoma: heterozygous deletion ofFrontiers in endocrinology · 2024Article
- Mof plays distinct roles in hepatic lipid metabolism under healthy or non-alcoholic fatty liver conditions.iScience · 2023Article
- The million-molecule challenge: a moonshot project to rapidly advance longevity intervention discovery.GeroScience · 2023Article
- Chronic high-sugar diet in adulthood protects Caenorhabditis elegans from 6-OHDA-induced dopaminergic neurodegeneration.BMC biology · 2023Article
- Endocrine, genetic, and microbiome nexus of obesity and potential role of postbiotics: a narrative review.Eating and weight disorders : EWD · 2023Review
- Article
- Malic Enzyme 1 (ME1) Promotes Adiposity and Hepatic Steatosis and Induces Circulating Insulin and Leptin in Obese Female Mice.International journal of molecular sciences · 2023Article
- The Importance of Animal Models in Biomedical Research: Current Insights and Applications.Animals : an open access journal from MDPI · 2023Review
- Single-cell chromatin accessibility profiling of cell-state-specific gene regulatory programs during mouse organogenesis.Frontiers in neuroscience · 2023Article
- Obesity III: Obesogen assays: Limitations, strengths, and new directions.Biochemical pharmacology · 2022Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Obesity and its associated metabolic syndrome are a leading cause of morbidity and mortality. Given the disease's heavy burden on patients and the healthcare system, there has been increased interest in identifying pharmacological targets for the treatment and prevention of obesity. Towards this end, genome-wide association studies (GWAS) have identified hundreds of human genetic variants associated with obesity. The next challenge is to experimentally define which of these variants are causally linked to obesity, and could therefore become targets for the treatment or prevention of obesity. Here we employ high-throughput in vivo RNAi screening to test for causality 293 C. elegans orthologs of human obesity-candidate genes reported in GWAS. We RNAi screened these 293 genes in C. elegans subject to two different feeding regimens: (1) regular diet, and (2) high-fructose diet, which we developed and present here as an invertebrate model of diet-induced obesity (DIO). We report 14 genes that promote obesity and 3 genes that prevent DIO when silenced in C. elegans. Further, we show that knock-down of the 3 DIO genes not only prevents excessive fat accumulation in primary and ectopic fat depots but also improves the health and extends the lifespan of C. elegans overconsuming fructose. Importantly, the direction of the association between expression variants in these loci and obesity in mice and humans matches the phenotypic outcome of the loss-of-function of the C. elegans ortholog genes, supporting the notion that some of these genes would be causally linked to obesity across phylogeny. Therefore, in addition to defining causality for several genes so far merely correlated with obesity, this study demonstrates the value of model systems compatible with in vivo high-throughput genetic screening to causally link GWAS gene candidates to human diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.