APPL1 transgenic mice are protected from high-fat diet-induced cardiac dysfunction
| Autor: | Cheolsoo Choi, Min Park, Ren-Ke Li, Aimin Xu, Gary Sweeney, Donghai Wu, Kenneth K.Y. Cheng, Tae-Sik Park |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Cardiac function curve
medicine.medical_specialty Ceramide Physiology Endocrinology Diabetes and Metabolism Transgene Glucose uptake medicine.medical_treatment Mice Transgenic Biology Diet High-Fat chemistry.chemical_compound Mice Physiology (medical) Internal medicine medicine Animals Insulin Myocytes Cardiac Adaptor Proteins Signal Transducing Glucose tolerance test Adiponectin medicine.diagnostic_test Body Weight food and beverages Glucose Tolerance Test Lipids Endocrinology Glucose chemistry Lipotoxicity lipids (amino acids peptides and proteins) Insulin Resistance Cardiomyopathies Proto-Oncogene Proteins c-akt |
| Zdroj: | American journal of physiology. Endocrinology and metabolism. 305(7) |
| ISSN: | 1522-1555 |
| Popis: | APPL1 (adaptor protein containing PH domain, PTB domain, and leucine zipper motif 1) has been established as an important mediator of insulin and adiponectin signaling. Here, we investigated the influence of transgenic (Tg) APPL1 overexpression in mice on high-fat diet (HFD)-induced cardiomyopathy in mice. Wild-type (WT) mice fed an HFD for 16 wk showed cardiac dysfunction, determined by echocardiography, with decreased ejection fraction, decreased fractional shortening, and increased end diastolic volume. HFD-fed APPL1 Tg mice were significantly protected from this dysfunction. Speckle tracking echocardiography to accurately assess cardiac tissue deformation strain and wall motion also indicated dysfunction in WT mice and a similar improvement in Tg vs. WT mice on HFD. APPL1 Tg mice had less HFD-induced increase in circulating nonesteridied fatty acid levels and myocardial lipid accumulation. Lipidomic analysis using LC-MS-MS showed HFD significantly increased myocardial contents of distinct ceramide, sphingomyelin, and diacylglycerol (DAG) species, of which increases in C16:0 and C18:0 ceramides plus C16:0 and C18:1 DAGs were attenuated in Tg mice. A glucose tolerance test indicated less peripheral insulin resistance in response to HFD in Tg mice, which was also apparent by measuring cardiac Akt phosphorylation and cardiomyocyte glucose uptake. In summary, APPL1 Tg mice exhibit improved peripheral metabolism, reduced cardiac lipotoxicity, and improved insulin sensitivity. These cellular effects contribute to protection from HFD-induced cardiomyopathy. |
| Databáze: | OpenAIRE |
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