ArticleCardiovascular diabetology2016
TNF-α induces vascular insulin resistance via positive modulation of PTEN and decreased Akt/eNOS/NO signaling in high fat diet-fed mice.
Article in Cardiovascular diabetology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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53 citing papers in PubMed, 98 citations in OpenAlex.
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- Comparing Methods for Induction of Insulin Resistance in Mouse 3T3-L1 Cells.Current diabetes reviews · 2025Article
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- Exploring the Antidiabetic Potential ofPlants (Basel, Switzerland) · 2024Article
- Long-Term Exposure to Polystyrene Microspheres and High-Fat Diet-Induced Obesity in Mice: Evaluating a Role for Microbiota Dysbiosis.Environmental health perspectives · 2024Article
- Perivascular Adipose Tissue and Uterine Artery Adaptations to Pregnancy.Microcirculation (New York, N.Y. : 1994) · 2024Review
- In utero exposure to maternal diabetes exacerbates dietary sodium intake-induced endothelial dysfunction by activating cyclooxygenase 2-derived prostanoids.American journal of physiology. Endocrinology and metabolism · 2024Article
- Demographic risk factors of pro-inflammatory diet: a narrative review.Frontiers in nutrition · 2024Review
- Cardiovascular dysfunction induced by combined exposure to nicotine inhalation and high-fat diet.American journal of physiology. Heart and circulatory physiology · 2024Article
- Mechanism of YJKL Decoction in Treating of PCOS Infertility by Integrative Approach of Network Pharmacology and Experimental Verification.Drug design, development and therapy · 2024Article
- The Role of Perivascular Adipose Tissue in the Pathogenesis of Endothelial Dysfunction in Cardiovascular Diseases and Type 2 Diabetes Mellitus.Biomedicines · 2023Review
- Suppressed vascular Rho-kinase activation is a protective cardiovascular mechanism in obese female mice.Bioscience reports · 2023Article
- Molecular Mechanisms for the Vicious Cycle between Insulin Resistance and the Inflammatory Response in Obesity.International journal of molecular sciences · 2023Review
- Increased hepatic Akt phosphorylation alleviated glucose intolerance and improved liver function in leptin-deficient mice.Clinical and experimental hepatology · 2023Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHigh fat diet (HFD) induces insulin resistance in various tissues, including the vasculature. HFD also increases plasma levels of TNF-α, a cytokine that contributes to insulin resistance and vascular dysfunction. Considering that the enzyme phosphatase and tension homologue (PTEN), whose expression is increased by TNF-α, reduces Akt signaling and, consequently, nitric oxide (NO) production, we hypothesized that PTEN contributes to TNF-α-mediated vascular resistance to insulin induced by HFD. Mechanisms underlying PTEN effects were determined.
methodsMesenteric vascular beds were isolated from C57Bl/6J and TNF-α KO mice submitted to control or HFD diet for 18 weeks to assess molecular mechanisms by which TNF-α and PTEN contribute to vascular dysfunction.
resultsVasodilation in response to insulin was decreased in HFD-fed mice and in ex vivo control arteries incubated with TNF-α. TNF-α receptors deficiency and TNF-α blockade with infliximab abolished the effects of HFD and TNF-α on insulin-induced vasodilation. PTEN vascular expression (total and phosphorylated isoforms) was increased in HFD-fed mice. Treatment with a PTEN inhibitor improved insulin-induced vasodilation in HFD-fed mice. TNF-α receptor deletion restored PTEN expression/activity and Akt/eNOS/NO signaling in HFD-fed mice.
conclusionTNF-α induces vascular insulin resistance by mechanisms that involve positive modulation of PTEN and inhibition of Akt/eNOS/NO signaling. Our findings highlight TNF-α and PTEN as potential targets to limit insulin resistance and vascular complications associated with obesity-related conditions.
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