ArticleEndocrinology2014
Macrophage metalloelastase (MMP12) regulates adipose tissue expansion, insulin sensitivity, and expression of inducible nitric oxide synthase.
Article in Endocrinology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.
- Proteomic Markers of Aging and Longevity: A Systematic Review.International journal of molecular sciences · 2024Pooled it
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- Secreted Phosphoprotein 1 (SPP1) Modulates Intracellular Metabolic Programs in Mature Adipocytes Revealed by Untargeted Metabolomics.International journal of molecular sciences · 2026Article
- Cysteine-S-nitrosylation inhibits Rop5-mediated immune evasion inbioRxiv : the preprint server for biology · 2025Article
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- Implications of the Matrix Metalloproteinases, Their Tissue Inhibitors and Some Other Inflammatory Mediators Expression Levels in Children Obesity-Related Phenotypes.Journal of personalized medicine · 2024Article
- MMP-12 and Periodontitis: Unraveling the Molecular Pathways of Periodontal Tissue Destruction.Journal of inflammation research · 2024Review
- Genetic deletion of MMP12 ameliorates cardiometabolic disease by improving insulin sensitivity, systemic inflammation, and atherosclerotic features in mice.Cardiovascular diabetology · 2023Article
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- Roles of Matrix Metalloproteinases and Their Natural Inhibitors in Metabolism: Insights into Health and Disease.International journal of molecular sciences · 2023Review
- CXCR6 Mediates Pressure Overload-Induced Aortic Stiffness by Increasing Macrophage Recruitment and Reducing Exosome-miRNA29b.Journal of cardiovascular translational research · 2023Article
- Microbiota and adipocyte mitochondrial damage in type 2 diabetes are linked by Mmp12+ macrophages.The Journal of experimental medicine · 2022Article
- Blood protein profiles related to preterm birth and retinopathy of prematurity.Pediatric research · 2022Article
- The aberrant cross-talk of epithelium-macrophages via METTL3-regulated extracellular vesicle miR-93 in smoking-induced emphysema.Cell biology and toxicology · 2022Article
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- Genistein and exercise treatment reduced NASH related HDAC3, IL-13 and MMP-12 expressions in ovariectomized rats fed with high fat high fructose diet.Journal of traditional and complementary medicine · 2021Article
- The Impact of Obesity on Microglial Function: Immune, Metabolic and Endocrine Perspectives.Cells · 2021Review
- Immune-Associated Proteins Are Enriched in Lung Tissue-Derived Extracellular Vesicles during Allergen-Induced Eosinophilic Airway Inflammation.International journal of molecular sciences · 2021Article
- Brown Adipose Expansion and Remission of Glycemic Dysfunction in Obese SM/J Mice.Cell reports · 2020Article
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
Macrophage metalloelastase, a matrix metallopeptidase (MMP12) predominantly expressed by mature tissue macrophages, is implicated in pathological processes. However, physiological functions for MMP12 have not been described. Because mRNA levels for the enzyme increase markedly in adipose tissue of obese mice, we investigated the role of MMP12 in adipose tissue expansion and insulin resistance. In humans, MMP12 expression correlated positively and significantly with insulin resistance, TNF-α expression, and the number of CD14(+)CD206(+) macrophages in adipose tissue. MMP12 was the most abundant matrix metallopeptidase detected by proteomic analysis of conditioned medium of M2 macrophages and dendritic cells. In contrast, it was detected only at low levels in bone marrow derived macrophages and M1 macrophages. When mice received a high-fat diet, adipose tissue mass increased and CD11b(+)F4/80(+)CD11c(-) macrophages accumulated to a greater extent in MMP12-deficient (Mmp12(-/-)) mice than in wild-type mice (Mmp12(+/+)). Despite being markedly more obese, fat-fed Mmp12(-/-) mice were more insulin sensitive than fat-fed Mmp12(+/+) mice. Expression of inducible nitric oxide synthase (Nos2) by Mmp12(-/-) macrophages was significantly impaired both in vivo and in vitro, suggesting that MMP12 might mediate nitric oxide production during inflammation. We propose that MMP12 acts as a double-edged sword by promoting insulin resistance while combatting adipose tissue expansion.
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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 Socratic graph.