1. 1888-P: Activation of Myocardial Mitochondrial Akt1 Remotely Modulated Body Composition and Adiposity through LXR/RXR Signaling
- Author
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Yu-Han Chen, Yumay Chen, Albert Ta, Emily Tom, and Ping Wang
- Subjects
Genetically modified mouse ,medicine.medical_specialty ,business.industry ,Endocrinology, Diabetes and Metabolism ,AKT1 ,Type 2 diabetes ,medicine.disease ,Insulin resistance ,Endocrinology ,Internal medicine ,Heart failure ,Diabetic cardiomyopathy ,Internal Medicine ,medicine ,Liver X receptor ,business ,Protein kinase B - Abstract
Insulin resistance contributed to the development of type 2 diabetes (T2D) and is a major risk factor for diabetic cardiomyopathy (DCM). We have previously reported that insulin resistance led to impaired Akt1 translocation into myocardial mitochondria in DCM. To study the role of mitochondrial Akt1 in DCM, we have generated two cardiac-specific inducible Cre-lox transgenic mice models that expresses (1) a mitochondria-targeting dominant negative Akt (CAMDAKT) or (2) a mitochondria-targeting constitutively active Akt (CAMCAKT) upon Tamoxifen induction (T). T-CAMDAKT mice showed LV dysfunction with increased heart failure markers, while T-CAMCAKT mice restored LV dysfunction to normal in the T2D model. In a T2D model induced by high fat/high fructose diet with relative insulin deficiency, T-CAMCAKT mice showed lower body fat mass (16.6% vs. 26.5%, p Disclosure Y. Chen: None. A. Ta: None. E. Tom: None. Y. Chen: None. P.H. Wang: Board Member; Self; Dianavi. Funding National Institutes of Health (R01HL096987)
- Published
- 2020
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