Ceramide synthase 5 mediates lipid-induced autophagy and hypertrophy in cardiomyocytes
Sarah Brice Russo,Catalin F. Baicu,An O. Van Laer,Tuoyu Geng,Harinath Kasiganesan,Michael R. Zile,L. Ashley Cowart +6 more
TLDR
A requirement for a specific sphingolipid metabolic route and dietary SFAs in the molecular pathogenesis of lipotoxic cardiomyopathy and hypertrophy is revealed.Abstract:
Diabetic cardiomyopathy (DbCM), which consists of cardiac hypertrophy and failure in the absence of traditional risk factors, is a major contributor to increased heart failure risk in type 2 diabetes patients. In rodent models of DbCM, cardiac hypertrophy and dysfunction have been shown to depend upon saturated fatty acid (SFA) oversupply and de novo sphingolipid synthesis. However, it is not known whether these effects are mediated by bulk SFAs and sphingolipids or by individual lipid species. In this report, we demonstrate that a diet high in SFA induced cardiac hypertrophy, left ventricular systolic and diastolic dysfunction, and autophagy in mice. Furthermore, treatment with the SFA myristate, but not palmitate, induced hypertrophy and autophagy in adult primary cardiomyocytes. De novo sphingolipid synthesis was required for induction of all pathological features observed both in vitro and in vivo, and autophagy was required for induction of hypertrophy in vitro. Finally, we implicated a specific ceramide N-acyl chain length in this process and demonstrated a requirement for (dihydro)ceramide synthase 5 in cardiomyocyte autophagy and myristate-mediated hypertrophy. Thus, this report reveals a requirement for a specific sphingolipid metabolic route and dietary SFAs in the molecular pathogenesis of lipotoxic cardiomyopathy and hypertrophy.read more
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Mechanisms of physiological and pathological cardiac hypertrophy
TL;DR: The characteristics and underlying mechanisms of physiological and pathological hypertrophy are summarized, and possible therapeutic strategies targeting these pathways to prevent or reverse pathological hyperTrophy are discussed.
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Cardiac Metabolism and its Interactions With Contraction, Growth, and Survival of Cardiomyocytes
TL;DR: An overview of the cardiac metabolic network is provided and alterations observed in cardiac pathologies as well as strategies used as metabolic therapies in heart failure are highlighted.
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Intestinal farnesoid X receptor signaling promotes nonalcoholic fatty liver disease
Changtao Jiang,Changtao Jiang,Cen Xie,Fei Li,Limin Zhang,Robert G. Nichols,Kristopher W. Krausz,Jingwei Cai,Yunpeng Qi,Zhong-Ze Fang,Shogo Takahashi,Naoki Tanaka,Dhimant Desai,Shantu Amin,Istvan Albert,Andrew D. Patterson,Frank J. Gonzalez +16 more
TL;DR: It is demonstrated that inhibition of an intestinal FXR/ceramide axis mediates gut microbiota-associated NAFLD development, linking the microbiome, nuclear receptor signaling, andNAFLD.
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Ceramides – Lipotoxic Inducers of Metabolic Disorders
TL;DR: The need to further decipher the full array of benefits elicited by ceramide depletion is highlighted, suggesting that inhibiting ceramide biosynthesis or catalyzing ceramide degradation in rodents ameliorates many metabolic disorders including diabetes, cardiomyopathy, insulin resistance, atherosclerosis, and steatohepatitis.
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Diabetic cardiomyopathy: Mechanisms and new treatment strategies targeting antioxidant signaling pathways
Karina Huynh,Bianca C. Bernardo,Julie R. McMullen,Julie R. McMullen,Rebecca H. Ritchie,Rebecca H. Ritchie +5 more
TL;DR: This work reviews the current evidence of molecular disturbances present in the diabetic heart, and their role in the development of diabetes-induced impairments in myocardial function and structure, and incorporates both the contribution of increased reactive oxygen species production and reduced antioxidant defenses to diabetic cardiomyopathy.
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