ArticleThe Journal of clinical investigation2007
Hypotension, lipodystrophy, and insulin resistance in generalized PPARgamma-deficient mice rescued from embryonic lethality.
Article in The Journal of clinical investigation, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
98 citing papers in PubMed, 1 synthesis or guideline pooled it, 170 citations in OpenAlex.
- Peroxisome proliferator-activated receptor γ polymorphism Pro12Ala Is associated with nephropathy in type 2 diabetes: evidence from meta-analysis of 18 studies.Diabetes care · 2012Pooled it
- Conserved gene expression patterns in the placenta underlie pregnancy complications associated with hypoxia in mice and humans.Cellular and molecular life sciences : CMLS · 2026Article
- The Placenta Regulates Intrauterine Fetal Growth via Exosomal PPARγ.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Collecting duct NCOR1 controls blood pressure by regulating mineralocorticoid receptor.Journal of advanced research · 2025Article
- β'-COP mediated loading of PPARγ into trophoblast-derived extracellular vesicles.Cellular and molecular life sciences : CMLS · 2024Article
- Review
- Anti‑obesity and immunostimulatory activity ofExperimental and therapeutic medicine · 2024Article
- Review
- Alpha-lipoic acid upregulates the PPARγ/NRF2/GPX4 signal pathway to inhibit ferroptosis in the pathogenesis of unexplained recurrent pregnancy loss.Open medicine (Warsaw, Poland) · 2024Article
- Review
- The Role of Transcription Factor PPAR-γ in the Pathogenesis of Psoriasis, Skin Cells, and Immune Cells.International journal of molecular sciences · 2022Review
- How trophoblasts fuse: an in-depth look into placental syncytiotrophoblast formation.Cellular and molecular life sciences : CMLS · 2022Review
- Article
- Adipocyte Biology from the Perspective of In Vivo Research: Review of Key Transcription Factors.International journal of molecular sciences · 2021Review
- C1431T Variant of PPARγ Is Associated with Preeclampsia in Pregnant Women.Life (Basel, Switzerland) · 2021Article
- Critical roles of transcriptional coactivator MED1 in the formation and function of mouse adipose tissues.Genes & development · 2021Article
- Adipocyte-specific deletion of zinc finger protein 407 results in lipodystrophy and insulin resistance in mice.Molecular and cellular endocrinology · 2021Article
- Role of Peroxisome Proliferator-Activated Receptors (PPARs) in Trophoblast Functions.International journal of molecular sciences · 2021Review
- Deletion ofFrontiers in cardiovascular medicine · 2021Article
- Parsing the Role of PPARs in Macrophage Processes.Frontiers in immunology · 2021Review
38 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
We rescued the embryonic lethality of global PPARgamma knockout by breeding Mox2-Cre (MORE) mice with floxed PPARgamma mice to inactivate PPARgamma in the embryo but not in trophoblasts and created a generalized PPARgamma knockout mouse model, MORE-PPARgamma knockout (MORE-PGKO) mice. PPARgamma inactivation caused severe lipodystrophy and insulin resistance; surprisingly, it also caused hypotension. Paradoxically, PPARgamma agonists had the same effect. We showed that another mouse model of lipodystrophy was hypertensive, ruling out the lipodystrophy as a cause. Further, high salt loading did not correct the hypotension in MORE-PGKO mice. In vitro studies showed that the vasculature from MORE-PGKO mice was more sensitive to endothelial-dependent relaxation caused by muscarinic stimulation, but was not associated with changes in eNOS expression or phosphorylation. In addition, vascular smooth muscle had impaired contraction in response to alpha-adrenergic agents. The renin-angiotensin-aldosterone system was mildly activated, consistent with increased vascular capacitance or decreased volume. These effects are likely mechanisms contributing to the hypotension. Our results demonstrated that PPARgamma is required to maintain normal adiposity and insulin sensitivity in adult mice. Surprisingly, genetic loss of PPARgamma function, like activation by agonists, lowered blood pressure, likely through a mechanism involving increased vascular relaxation.
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What OpenQuestion holds
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.