ArticleNutrition & metabolism2019
An adiponectin-S1P axis protects against lipid induced insulin resistance and cardiomyocyte cell death via reduction of oxidative stress.
Article in Nutrition & metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 28 citations in OpenAlex.
- AdipoRon ameliorates the progression of heart failure with preserved ejection fraction via mitigating lipid accumulation and fibrosis.Journal of advanced research · 2025Article
- Aging alters the effect of adiponectin receptor signaling on bone marrow-derived mesenchymal stem cells.Aging cell · 2025Article
- Novel role of Quercetin in ameliorating metabolic syndrome via VDR mediated activation of adiponectin/AdipoR2 signaling.Biochemistry and biophysics reports · 2024Article
- Bile acid metabolism and signaling in health and disease: molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2024Review
- Small-molecule agonist AdipoRon alleviates diabetic retinopathy through the AdipoR1/AMPK/EGR4 pathway.Journal of translational medicine · 2024Article
- Elucidating the primary mechanisms of high-intensity interval training for improved cardiac fitness in obesity.Frontiers in physiology · 2023Review
- Sphingolipids in mitochondria-from function to disease.Frontiers in cell and developmental biology · 2023Review
- Adiponectin: friend or foe in obesity and inflammation.Medical review (2021) · 2022Review
- Article
- Ceramides and other sphingolipids as drivers of cardiovascular disease.Nature reviews. Cardiology · 2021Review
- Adiponectin Synthesis, Secretion and Extravasation from Circulation to Interstitial Space.Physiology (Bethesda, Md.) · 2021Review
- S1P Signaling Pathways in Pathogenesis of Type 2 Diabetes.Journal of diabetes research · 2021Article
- An adiponectin-S1P autocrine axis protects skeletal muscle cells from palmitate-induced cell death.Lipids in health and disease · 2020Article
- CTRP9 knockout exaggerates lipotoxicity in cardiac myocytes and high-fat diet-induced cardiac hypertrophy through inhibiting the LKB1/AMPK pathway.Journal of cellular and molecular medicine · 2020Article
- Adiponectin Decreases Gastric Smooth Muscle Cell Excitability in Mice.Frontiers in physiology · 2019Article
- Examining the Potential of Developing and Implementing Use of Adiponectin-Targeted Therapeutics for Metabolic and Cardiovascular Diseases.Frontiers in endocrinology · 2019Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAdiponectin exerts several beneficial cardiovascular effects, however their specific molecular mechanisms require additional understanding. This study investigated the mechanisms of adiponectin action in the heart during high fat diet (HFD) feeding or in palmitate (PA) treated H9c2 cardiomyoblasts.
methods6-week-old male adiponectin knock out (Ad-KO) mice were fed chow or 60% HFD for 6 weeks then received saline or recombinant adiponectin (3μg/g body weight) for an additional 2 weeks. After acute insulin stimulation (4 U/kg), tissue and serum samples were collected for analysis. H9c2 cardiomyocytes were treated ±0.1 mM PA, the adiponectin receptor agonist AdipoRon, or the antioxidant MnTBAP then assays to analyze reactive oxygen species (ROS) production and cell death were conducted. To specifically determine the mechanistic role of S1P, gain and loss of function studies were conducted with adding S1P to cells or the inhibitors THI and SKI-II, respectively.
resultsHFD feeding induced cardiac insulin resistance in Ad-KO mice, which was reversed following replenishment of normal circulating adiponectin levels. In addition, myocardial total triglyceride was elevated by HFD and lipidomic analysis showed increased levels of ceramides and sphingosine-1-phosphate (S1P), with only the latter being corrected by adiponectin administration. Similarly, treatment of H9C2 cardiomyoblasts with PA led to a significant increase of intracellular S1P but not in conditioned media whereas AdipoRon significantly increased S1P production and secretion from cells. AdipoRon or the antioxidant MnTBAP significantly reduced PA-induced cell death. Gain and loss of function studies suggested S1P secretion and autocrine receptor activation mediated the effect of AdipoRon to attenuate PA-induced ROS production and cell death.
conclusionOur data establish adiponectin signaling-mediated increase in S1P secretion as a mechanism via which HFD or PA induced cardiomyocyte lipotoxicity, leading to insulin resistance and cell death, is attenuated.
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