Inhibition of endoplasmic reticulum stress prevents high‐fat diet mediated atrial fibrosis and fibrillation

Zhang, Yan; Yang, Shuwen; Fu, Jing; Liu, Annan; Liu, Deping; Cao, Suyan

doi:10.1111/jcmm.15816

Cited by 13 publications

(6 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Obesity is an important risk factor for atrial fibrillation. Atrial fibrillation is the most common persistent arrhythmia and can cause morbidity and mortality [ 24 ]. To detect whether the hearts of obese Drosophila were abnormal, we performed semi-intact preparations and M-mode analysis.…”

Section: Resultsmentioning

confidence: 99%

Effects of Drosophila melanogaster regular exercise and apolipoprotein B knockdown on abnormal heart rhythm induced by a high-fat diet

Ding

Guo

et al. 2022

PLoS ONE

View full text Add to dashboard Cite

Abnormal heart rhythm is a common cardiac dysfunction in obese patients, and its pathogenesis is related to systemic lipid accumulation. The cardiomyocyte-derived apoLpp (homologous gene in Drosophila of the human apolipoprotein B) plays an important role in whole-body lipid metabolism of Drosophila under a high-fat diet (HFD). Knockdown of apoLpp derived from cardiomyocytes can reduce HFD-induced weight gain and abdominal lipid accumulation. In addition, exercise can reduce the total amount of apoLpp in circulation. However, the relationship between regular exercise, cardiomyocyte-derived apoLpp and abnormal heart rhythm is unclear. We found that an HFD increased the level of triglyceride (TG) in the whole-body, lipid accumulation and obesity in Drosophila. Moreover, the expression of apoLpp in the heart increased sharply, the heart rate and arrhythmia index increased and fibrillation occurred. Conversely, regular exercise or cardiomyocyte-derived apoLpp knockdown reduced the TG level in the whole-body of Drosophila. This significantly reduced the arrhythmia induced by obesity, including the reduction of heart rate, arrhythmia index, and fibrillation. Under HFD conditions, flies with apoLpp knockdown in the heart could resist the abnormal cardiac rhythm caused by obesity after receiving regular exercise. HFD-induced obesity and abnormal cardiac rhythm may be related to the acute increase of cardiomyocyte-derived apoLpp. Regular exercise and inhibition of cardiomyocyte-derived apoLpp can reduce the HFD-induced abnormal cardiac rhythm.

show abstract

Section: Resultsmentioning

confidence: 99%

Effects of Drosophila melanogaster regular exercise and apolipoprotein B knockdown on abnormal heart rhythm induced by a high-fat diet

Ding

Guo

et al. 2022

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…We found varying degrees of increase in HR, AI and FL ( Figure 3 A,C,F) under HFD compared to NFD. It is well-established that fibrillation is the most common sustained arrhythmia and a high-risk factor for morbidity and mortality due to obesity [ 34 ]. Significant decreases in HP,SI, DD and FS ( Figure 3 B,E,G,I) and diastolic diameter and fractional shortening indicated a decrease in myocardial contractility in Drosophila .…”

Section: Resultsmentioning

confidence: 99%

Exercise Training Upregulates Cardiac mtp Expression in Drosophila melanogaster with HFD to Improve Cardiac Dysfunction and Abnormal Lipid Metabolism

Peng

Ding

Yan

et al. 2022

Biology

View full text Add to dashboard Cite

Current evidence suggests that the heart plays an important role in regulating systemic lipid homeostasis, and high-fat diet (HFD)-induced obesity is a major cause of cardiovascular disease, although little is known about the specific mechanisms involved. Exercise training can reportedly improve abnormal lipid metabolism and cardiac dysfunction induced by high-fat diets; however, the molecular mechanisms are not yet understood. In the present study, to explore the relationship between exercise training and cardiac mtp in HFD flies and potential mechanisms by which exercise training affects HFD flies, Drosophila was selected as a model organism, and the GAL4/UAS system was used to specifically knock down the target gene. Experiments revealed that HFD-fed Drosophila exhibited changes in body weight, increased triglycerides (TG) and dysregulated cardiac contractility, consistent with observations in mammals. Interestingly, inhibition of cardiac mtp expression reduced HFD-induced cardiac damage and mitigated the increase in triglycerides. Further studies showed that in HFD +w1118, HFD + Hand > w1118, and HFD+ Hand > mtpRNAi, cardiac mtp expression downregulation induced by HFD was treated by exercise training and mitochondrial β-oxidation capacity in cardiomyocytes was reversed. Overall, knocking down mtp in the heart prevented an increase in systemic TG levels and protected cardiac contractility from damage caused by HFD, similar to the findings observed after exercise training. Moreover, exercise training upregulated the decrease in cardiac mtp expression induced by HFD. Increased Had1 and Acox3 expression were observed, consistent with changes in cardiac mtp expression.

show abstract

“…Obese patients showed cardiac hypertrophy, LA dilation, atrial fibrosis and inflammation, 33 contributing to AF triggering and progression. Growing evidence proves HFD‐induced obesity also causes atrial inflammation and fibrosis, mediating atrial remodeling and AF in animal models 34‐37 . Thus, we fed mice HFD containing 60 kcal% fat to mimic obesity and established an obesity‐induced mouse AF model.…”

Section: Discussionmentioning

confidence: 99%

Necroptosis is required for atrial fibrillation and involved in aerobic exercise‐conferred cardioprotection

Jiang

Sun

et al. 2021

J Cellular Molecular Medi

View full text Add to dashboard Cite

Necroptosis, a novel programmed cell death, plays a critical role in the development of fibrosis, yet its role in atrial fibrillation (AF) remains elusive. Mounting evidence demonstrates that aerobic exercise improves AF‐related symptoms and quality of life. Therefore, we explored the role of necroptosis in AF pathogenesis and exercise‐conferred cardioprotection. A mouse AF model was established either by calcium chloride and acetylcholine (CaCl2‐Ach) administration for 3 weeks or high‐fat diet (HFD) feeding for 12 weeks, whereas swim training was conducted 60 min/day, for 3‐week duration. AF susceptibility, heart morphology and function and atrial fibrosis were assessed by electrophysiological examinations, echocardiography and Masson's trichrome staining, respectively. Both CaCl2‐Ach administration and HFD feeding significantly enhanced AF susceptibility (including frequency and duration of episodes), left atrial enlargement and fibrosis. Moreover, protein levels of necroptotic signaling (receptor‐interacting protein kinase 1, receptor‐interacting protein kinase 3, mixed lineage kinase domain‐like protein and calcium/calmodulin‐dependent protein kinase II or their phosphorylated forms) were markedly elevated in the atria of AF mice. However, inhibiting necroptosis with necrostatin‐1 partly attenuated CaCl2‐Ach (or HFD)‐induced fibrosis and AF susceptibility, implicating necroptosis as contributing to AF pathogenesis. Finally, we found 3‐week swim training inhibited necroptotic signaling, consequently decreasing CaCl2‐Ach‐induced AF susceptibility and atrial structural remodeling. Our findings identify necroptosis as a novel mechanism in AF pathogenesis and highlight that aerobic exercise may confer benefits on AF via inhibiting cardiac necroptosis.

show abstract

Inhibition of endoplasmic reticulum stress prevents high‐fat diet mediated atrial fibrosis and fibrillation

Cited by 13 publications

References 28 publications

Effects of Drosophila melanogaster regular exercise and apolipoprotein B knockdown on abnormal heart rhythm induced by a high-fat diet

Effects of Drosophila melanogaster regular exercise and apolipoprotein B knockdown on abnormal heart rhythm induced by a high-fat diet

Exercise Training Upregulates Cardiac mtp Expression in Drosophila melanogaster with HFD to Improve Cardiac Dysfunction and Abnormal Lipid Metabolism

Necroptosis is required for atrial fibrillation and involved in aerobic exercise‐conferred cardioprotection

Contact Info

Product

Resources

About