ArticleAmerican journal of physiology. Endocrinology and metabolism2017
Map4k4 impairs energy metabolism in endothelial cells and promotes insulin resistance in obesity.
Article in American journal of physiology. Endocrinology and metabolism, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
9 citing papers in PubMed, 27 citations in OpenAlex.
- Treating Metabolic Dysregulation and Senescence by Caloric Restriction: Killing Two Birds with One Stone?Antioxidants (Basel, Switzerland) · 2025Review
- Role of Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 Signaling in Liver and Metabolic Diseases.The Journal of pharmacology and experimental therapeutics · 2024Review
- MAP4K4 exacerbates cardiac microvascular injury in diabetes by facilitating S-nitrosylation modification of Drp1.Cardiovascular diabetology · 2024Article
- Overcoming radioresistance of breast cancer cells with MAP4K4 inhibitors.Scientific reports · 2024Article
- Article
- Capillary Rarefaction in Obesity and Metabolic Diseases-Organ-Specificity and Possible Mechanisms.Cells · 2020Review
- Comparative proteomic analysis of SLC13A5 knockdown reveals elevated ketogenesis and enhanced cellular toxic response to chemotherapeutic agents in HepG2 cells.Toxicology and applied pharmacology · 2020Article
- Insulin resistance disrupts cell integrity, mitochondrial function, and inflammatory signaling in lymphatic endothelium.Microcirculation (New York, N.Y. : 1994) · 2018Article
- Vascular Endothelial Regulation of Obesity-Associated Insulin Resistance.Frontiers in cardiovascular medicine · 2017Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The blood vasculature responds to insulin, influencing hemodynamic changes in the periphery, which promotes tissue nutrient and oxygen delivery and thus metabolic function. The lymphatic vasculature regulates fluid and lipid homeostasis, and impaired lymphatic function can contribute to atherosclerosis and obesity. Recent studies have suggested a role for endothelial cell (EC) mitogen-activated protein kinase kinase kinase kinase 4 (Map4k4) in developmental angiogenesis and lymphangiogenesis as well as atherosclerosis. Here, we show that inducible EC Map4k4 deletion in adult mice ameliorates metabolic dysfunction in obesity despite the development of chylous ascites and a concomitant striking increase in adipose tissue lymphocyte content. Despite these defects, animals lacking endothelial Map4k4 were protected from skeletal muscle microvascular rarefaction in obesity, and primary ECs lacking Map4k4 displayed reduced senescence and increased metabolic capacity. Thus endothelial Map4k4 has complex and opposing functions in the blood and lymphatic endothelium postdevelopment. Whereas blood endothelial Map4k4 promotes vascular dysfunction and impairs glucose homeostasis in adult animals, lymphatic endothelial Map4k4 is required to maintain lymphatic vascular integrity and regulate immune cell trafficking in obesity.
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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.