ArticleProceedings of the National Academy of Sciences of the United States of America2015
Plexin D1 determines body fat distribution by regulating the type V collagen microenvironment in visceral adipose tissue.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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43 citing papers in PubMed, 71 citations in OpenAlex.
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- Zebrafish as a Model for Cardiovascular and Metabolic Disease: The Future of Precision Medicine.Biomedicines · 2024Review
- Gestational Caloric Restriction Alters Adipose Tissue Methylome and Offspring's Metabolic Profile in a Swine Model.International journal of molecular sciences · 2024Article
- Integrated analysis of muscle lncRNA and mRNA of Chinese indigenous breed Ningxiang pig in four developmental stages.Frontiers in veterinary science · 2024Article
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- Plexin D1 mediates disturbed flow-induced M1 macrophage polarization in atherosclerosis.Heliyon · 2023Article
- Identification of crucial modules and genes associated with backfat tissue development by WGCNA in Ningxiang pigs.Frontiers in genetics · 2023Article
- The potential inhibitory effect of ginsenoside Rh2 on mitophagy in UV-irradiated human dermal fibroblasts.Journal of ginseng research · 2022Article
- Adipocyte-Specific Laminin Alpha 4 Deletion Preserves Adipose Tissue Health despite Increasing Adiposity.Biomedicines · 2022Article
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- Insights into in vivo adipocyte differentiation through cell-specific labeling in zebrafish.Biology open · 2021Article
- Systems genetic analysis of binge-like eating in a C57BL/6J x DBA/2J-F2 cross.Genes, brain, and behavior · 2021Article
- Causal associations of waist circumference and waist-to-hip ratio with type II diabetes mellitus: new evidence from Mendelian randomization.Molecular genetics and genomics : MGG · 2021Article
- OSBPL2 Is Required for the Binding of COPB1 to ATGL and the Regulation of Lipid Droplet Lipolysis.iScience · 2020Article
- RSPO3 impacts body fat distribution and regulates adipose cell biology in vitro.Nature communications · 2020Article
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Authors and funding
9 authors at 6 institutions in 3 countries.
Funding
Abstract
Genome-wide association studies have implicated PLEXIN D1 (PLXND1) in body fat distribution and type 2 diabetes. However, a role for PLXND1 in regional adiposity and insulin resistance is unknown. Here we use in vivo imaging and genetic analysis in zebrafish to show that Plxnd1 regulates body fat distribution and insulin sensitivity. Plxnd1 deficiency in zebrafish induced hyperplastic morphology in visceral adipose tissue (VAT) and reduced lipid storage. In contrast, subcutaneous adipose tissue (SAT) growth and morphology were unaffected, resulting in altered body fat distribution and a reduced VAT:SAT ratio in zebrafish. A VAT-specific role for Plxnd1 appeared conserved in humans, as PLXND1 mRNA was positively associated with hypertrophic morphology in VAT, but not SAT. In zebrafish plxnd1 mutants, the effect on VAT morphology and body fat distribution was dependent on induction of the extracellular matrix protein collagen type V alpha 1 (col5a1). Furthermore, after high-fat feeding, zebrafish plxnd1 mutant VAT was resistant to expansion, and excess lipid was disproportionately deposited in SAT, leading to an even greater exacerbation of altered body fat distribution. Plxnd1-deficient zebrafish were protected from high-fat-diet-induced insulin resistance, and human VAT PLXND1 mRNA was positively associated with type 2 diabetes, suggesting a conserved role for PLXND1 in insulin sensitivity. Together, our findings identify Plxnd1 as a novel regulator of VAT growth, body fat distribution, and insulin sensitivity in both zebrafish and humans.
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