Jiung-Pang Huang1, Mei-Ling Cheng2, Chao-Hung Wang3, Ming-Shi Shiao1, Jan-Kan Chen4, Li-Man Hung5. 1. Department of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan; Center for Healthy and Aging Research, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan; Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan. 2. Department of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan; Center for Healthy and Aging Research, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan; Heart Failure Center, Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan; Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan. 3. Heart Failure Center, Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan. 4. Center for Healthy and Aging Research, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan; Department of Physiology and Pharmacology, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan. 5. Department of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan; Center for Healthy and Aging Research, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan; Heart Failure Center, Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan; Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan. Electronic address: lisahung@mail.cgu.edu.tw.
Abstract
BACKGROUND: The heart is a highly adaptive organ that demonstrates remarkable structural, functional, and metabolic remodeling in response to physiological and pathological stimuli. We hypothesize that the heart undergoes differential adaptations in high-fat and high-fructose diet, resulting in a distinct phenotype. METHODS: High-fat and high-fructose diet-induced obese and non-obese insulin resistance (IR) rat models were used to understand how the heart adapts to long-term (12-week) overnutrition. RESULTS: Rats fed the high-fat diet developed obese IR, whereas high-fructose diet developed non-obese IR. Obese IR rats developed fibrotic hypertrophy with impairment of preload-independent contractility. The sympathetic and renin-angiotensin-aldosterone (RAA) systems and myocardial adrenergic signaling were activated in obese IR rats. Non-obese IR rats developed apoptotic cardiomyopathy with severe systolic dysfunction. Myocardial calcium cycling regulatory proteins (CCRPs) were dysregulated in non-obese IR rats; specifically, troponin I protein expression was downregulated. Moreover, compared with the controls, lipidomics analysis revealed substantial differences in lipid metabolites in non-obese IR and obese IR rats. The overproduction of lysophosphatidylcholine (lysoPC) and fatty acids was observed in non-obese IR rat hearts. A strong correlation was observed between the myocardial lysoPC and plasma troponin I levels. Treatment of cardiomyocytes with lysoPC resulted in cell death in a dose- and time-dependent manner. The overproduction of myocardial lysoPCs was associated with circulating sPLA2 levels. CONCLUSION: Obese IR rats developed severe fibrotic hypertrophy with the activation of adrenergic signaling and sympathetic and RAA systems. The sPLA2-lysoPC may play a crucial role in the induction of apoptotic cardiomyopathy in high fructose-induced non-obese IR rats.
BACKGROUND: The heart is a highly adaptive organ that demonstrates remarkable structural, functional, and metabolic remodeling in response to physiological and pathological stimuli. We hypothesize that the heart undergoes differential adaptations in high-fat and high-fructose diet, resulting in a distinct phenotype. METHODS: High-fat and high-fructose diet-induced obese and non-obese insulin resistance (IR) rat models were used to understand how the heart adapts to long-term (12-week) overnutrition. RESULTS:Rats fed the high-fat diet developed obese IR, whereas high-fructose diet developed non-obese IR. Obese IR rats developed fibrotic hypertrophy with impairment of preload-independent contractility. The sympathetic and renin-angiotensin-aldosterone (RAA) systems and myocardial adrenergic signaling were activated in obese IR rats. Non-obese IR rats developed apoptotic cardiomyopathy with severe systolic dysfunction. Myocardial calcium cycling regulatory proteins (CCRPs) were dysregulated in non-obese IR rats; specifically, troponin I protein expression was downregulated. Moreover, compared with the controls, lipidomics analysis revealed substantial differences in lipid metabolites in non-obese IR and obese IR rats. The overproduction of lysophosphatidylcholine (lysoPC) and fatty acids was observed in non-obese IR rat hearts. A strong correlation was observed between the myocardial lysoPC and plasma troponin I levels. Treatment of cardiomyocytes with lysoPC resulted in cell death in a dose- and time-dependent manner. The overproduction of myocardial lysoPCs was associated with circulating sPLA2 levels. CONCLUSION:Obese IR rats developed severe fibrotic hypertrophy with the activation of adrenergic signaling and sympathetic and RAA systems. The sPLA2-lysoPC may play a crucial role in the induction of apoptotic cardiomyopathy in high fructose-induced non-obese IR rats.
Authors: Haneen S Dwaib; Ghina Ajouz; Ibrahim AlZaim; Rim Rafeh; Ali Mroueh; Nahed Mougharbil; Marie-Elizabeth Ragi; Marwan Refaat; Omar Obeid; Ahmed F El-Yazbi Journal: J Am Heart Assoc Date: 2021-12-07 Impact factor: 6.106