scholarly journals Shengmai San Alleviates Diabetic Cardiomyopathy Through Improvement of Mitochondrial Lipid Metabolic Disorder

2018 ◽  
Vol 50 (5) ◽  
pp. 1726-1739 ◽  
Author(s):  
Jing Tian ◽  
Wenzhu Tang ◽  
Ming Xu ◽  
Chen Zhang ◽  
Pei Zhao ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Diastolic Dysfunction ◽  
Diabetic Cardiomyopathy ◽  
Leptin Receptor ◽  
Myocardial Hypertrophy ◽  
Oxphos Complex ◽  
H9c2 Cardiomyocytes ◽  
Mitochondrial Lipid ◽  
And Function ◽  
Shengmai San

Background/Aims: Shengmai San (SMS), prepared from Panax ginseng, Ophiopogon japonicus, and Schisandra chinensisin, has been widely used to treat ischemic disease. In this study, we investigated whether SMS may exert a beneficial effect in diabetic cardiomyopathy through improvement of mitochondrial lipid metabolism. Methods: A leptin receptor-deficient db/db mouse model was utilized, and lean age-matched C57BLKS mice served as non-diabetic controls. Glucose and lipid profiles, myocardial structure, dimension, and function, and heart weight to tibial length ratio were determined. Myocardial ultrastructural morphology was observed with transmission electron microscopy. Protein expression and activity of oxidative phosphorylation (OXPHOS) complex were assessed using western blotting and microplate assay kits. We also observed cellular viability, mitochondrial membrane potential, OXPHOS complex activity, and cellular ATP level in palmitic acid-stimulated H9C2 cardiomyocytes. Changes in the sirtuin (SIRT1)/AMP-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) pathway and mitochondrial uncoupling signaling were assessed using western blotting and quantitative real-time PCR. Results: Leptin receptor-deficient db/db mice exhibit obesity, hyperglycemia, and hyperlipidemia, accompanied by distinct myocardial hypertrophy and diastolic dysfunction. SMS at a dose of 3 g/kg body weight contributed to a recovery of diabetes-induced myocardial hypertrophy and diastolic dysfunction. SMS administration led to an effective restoration of mitochondrial structure and function both in vivo and in vitro. Furthermore, SMS markedly enhanced SIRT1 and p-AMPKα protein levels and decreased the expression of acetylated-PGC-1α and uncoupling protein 2 protein. SMS also restored the depletion of NRF1 and TFAM levels in diabetic hearts and H9C2 cardiomyocytes. Conclusion: The results indicate that SMS may alleviate diabetes-induced myocardial hypertrophy and diastolic dysfunction by improving mitochondrial lipid metabolism.

scholarly journals Genetic Ablation of Calcium-independent Phospholipase A2γ Leads to Alterations in Mitochondrial Lipid Metabolism and Function Resulting in a Deficient Mitochondrial Bioenergetic Phenotype

2007 ◽  
Vol 282 (48) ◽  
pp. 34611-34622 ◽  
Author(s):  
David J. Mancuso ◽  
Harold F. Sims ◽  
Xianlin Han ◽  
Christopher M. Jenkins ◽  
Shao Ping Guan ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Genetic Ablation ◽  
Mitochondrial Lipid ◽  
And Function

scholarly journals The metabolic hormone leptin promotes the function of TFH cells and supports vaccine responses

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jun Deng ◽  
Qian Chen ◽  
Zhian Chen ◽  
Kaili Liang ◽  
Xin Gao ◽  
...  
Keyword(s):  
Leptin Receptor ◽  
Serum Levels ◽  
Affinity Maturation ◽  
Antibody Responses ◽  
Vaccine Failure ◽  
Vaccine Responses ◽  
Follicular Helper ◽  
B Virus ◽  
And Function ◽  
Metabolic Hormone

AbstractFollicular helper T (TFH) cells control antibody responses by supporting antibody affinity maturation and memory formation. Inadequate TFH function has been found in individuals with ineffective responses to vaccines, but the mechanism underlying TFH regulation in vaccination is not understood. Here, we report that lower serum levels of the metabolic hormone leptin associate with reduced vaccine responses to influenza or hepatitis B virus vaccines in healthy populations. Leptin promotes mouse and human TFH differentiation and IL-21 production via STAT3 and mTOR pathways. Leptin receptor deficiency impairs TFH generation and antibody responses in immunisation and infection. Similarly, leptin deficiency induced by fasting reduces influenza vaccination-mediated protection for the subsequent infection challenge, which is mostly rescued by leptin replacement. Our results identify leptin as a regulator of TFH cell differentiation and function and indicate low levels of leptin as a risk factor for vaccine failure.

scholarly journals Differences between diabetic and non-diabetic nephropathy patients in cardiac structure and function at the beginning of hemodialysis and their impact on the prediction of mortality

2021 ◽  
Vol 49 (3) ◽  
pp. 030006052199758
Author(s):  
Chao Tang ◽  
Han Ouyang ◽  
Jian Huang ◽  
Jing Zhu ◽  
Xiaosong Gu
Keyword(s):  
Diabetic Nephropathy ◽  
Diastolic Dysfunction ◽  
Peak Velocity ◽  
Structure And Function ◽  
Cardiac Valve ◽  
Cardiac Structure ◽  
Prediction Of Mortality ◽  
Cardiac Structure And Function ◽  
Lv Diastolic Dysfunction ◽  
And Function

Objectives To characterize differences in cardiac structure and function in hemodialysis (HD) patients with diabetic nephropathy (DN) and in those without using echocardiography and to determine their impact on the prediction of mortality using echocardiographic parameters. Methods Clinical, laboratory, and echocardiographic data were collected from patients commencing HD. Results Compared with those without DN, patients with DN had lower peak velocity of the early diastolic wave (e′), larger left atria, and higher peak early diastolic velocity (E)/e′ and peak velocity of tricuspid regurgitation (TR). In addition, a larger proportion of DN patients had a combination of left ventricular (LV) diastolic dysfunction, cardiac valve calcification, moderate-to-severe cardiac valve regurgitation (CVR), and at least moderate pericardial effusion (PE). After accounting for age, sex, smoking, hypertension, hemoglobin, and albumin, DN was responsible for e′  < 10 cm/s, E/e′ >13 m/s, TR >2.8 m/s, LV diastolic dysfunction, CVR, and PE. LV diastolic dysfunction and E/e′ >13 were the most useful predictors of mortality in patients with DN. Conclusions Patients with DN who undergo HD tend to have worse LV diastolic function and are more likely to have heart valve problems. LV diastolic dysfunction and E/e′ are predictors of death in DN patients.

scholarly journals Impact of obesity and SARS-CoV-2 infection: implications for host defence - a living review

2021 ◽  
Vol 2 (1) ◽  
Author(s):  
Felix Clemens Richter ◽  
Aljawharah Alrubayyi ◽  
Alicia Teijeira Crespo ◽  
Sarah Hulin-Curtis ◽  
Keyword(s):  
Lipid Metabolism ◽  
Influenza A ◽  
Immune Cell ◽  
Cell Metabolism ◽  
Low Grade ◽  
Obese Patients ◽  
Healthy Weight ◽  
Virus Infections ◽  
Immune Alterations ◽  
And Function

Abstract The role of obesity in the pathophysiology of respiratory virus infections has become particularly apparent during the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, where obese patients are twice as likely to suffer from severe coronavirus disease 2019 (COVID-19) than healthy weight individuals. Obesity results in disruption of systemic lipid metabolism promoting a state of chronic low-grade inflammation. However, it remains unclear how these underlying metabolic and cellular processes promote severe SARS-CoV-2 infection. Emerging data in SARS-CoV-2 and Influenza A virus (IAV) infections show that viruses can further subvert the host’s altered lipid metabolism and exploit obesity-induced alterations in immune cell metabolism and function to promote chronic inflammation and viral propagation. In this review, we outline the systemic metabolic and immune alterations underlying obesity and discuss how these baseline alterations impact the immune response and disease pathophysiology. A better understanding of the immunometabolic landscape of obese patients may aid better therapies and future vaccine design.

Abstract 17266: Right Atrial Volumes Changes in Tetralogy of Fallot

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_1) ◽  
Author(s):  
Ashish Patel ◽  
Divya Shakti ◽  
Chad Blackshear
Keyword(s):  
Diastolic Dysfunction ◽  
Diastolic Function ◽  
Tetralogy Of Fallot ◽  
Surgical Repair ◽  
Left Ventricular ◽  
Right Atrial ◽  
Before And After ◽  
Ventricular Diastolic Dysfunction ◽  
And Function ◽  
Averaged Model

Introduction & Hypothesis: There is limited information on right atrial (RA) function in the congenital heart defects. RA volume and function may give insight into the right ventricle (RV) diastolic function. We sought to assess RA function in tetralogy of Fallot (TOF) patients prior to and after complete surgical repair. Methods: Infants with TOF prior to complete repair were included for retrospective chart review and offline analysis of 2-dimensional echocardiograms (echo) before and after surgical repair. RA phasic volumes and stroke volumes were calculated. All volumes were indexed to body surface area. Results: There were 40 infants with TOF (45% females), of which 70% had pulmonary stenosis, 30% pulmonary atresia. Roughly 85% and 60% had 3, or more, echo available pre- and postoperatively. Table 1 (attached) shows the patient characteristics and phasic RA volumes. The indexed RA phasic volumes were in normal range in initial echo prior to surgery. We used normal index RA phasic volumes published by European Society of Echocardiography. There was the increasing trend of indexed RA phasic volume on follow up echo immediately before TOF repair. These phasic volumes continued to remain elevated after complete surgical repair (Table 1). Trends in RA stroke volumes for all available echos before and after surgery were modeled using a population-averaged model with an exchangeable within-panel correlation structure (Figure 2), showing no statistically significant difference after surgery. But there was statistical significance noted in RA ejection fraction. Please see attached image for statistical analysis and results of the study. Conclusions: The indexed RA phasic volumes in children with TOF are normal initially and increases before TOF repair and it continued to increase after TOF repair. The increase RA phasic volumes suggest RV diastolic dysfunction similar to the findings of LA phasic volumes and left ventricular diastolic dysfunction. Our findings indicate slow worsening RV diastolic function in patients with TOF after surgical repair. RA volume and function can be the novel marker to diagnose and monitor right ventricular diastolic dysfunction.

Abstract 16485: The Nitroxyl Donor 1-Nitrosocyclohexyl Acetate Limits Cardiac Superoxide Upregulation and Diastolic Dysfunction in a Mouse Model of Diabetic Cardiomyopathy

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Rebecca H Ritchie ◽  
Nga Cao ◽  
Yung George Wong ◽  
Sarah Rosli ◽  
Helen Kiriazis ◽  
...  
Keyword(s):  
Heart Failure ◽  
Mouse Model ◽  
Diastolic Dysfunction ◽  
Diabetic Cardiomyopathy ◽  
Ex Vivo ◽  
Systolic Function ◽  
Left Ventricular ◽  
Cardiomyocyte Hypertrophy ◽  
Lv Diastolic Dysfunction ◽  
The Impact

Nitroxyl (HNO), a redox congener of NO•, is a novel regulator of cardiovascular function combining vasodilator and positive inotropic properties. Our previous studies have demonstrated these properties occur concomitantly in the intact heart; HNO moreover also exhibits antihypertrophic and superoxide-suppressing actions. HNO donors may thus offer favorable actions in heart failure. The impact of chronic HNO donor administration has however yet to be reported in this context. We tested the hypothesis that the HNO donor 1-nitrosocyclohexyl acetate (1-NCA) limits cardiomyocyte hypertrophy and left ventricular (LV) diastolic dysfunction in a mouse model of diabetic cardiomyopathy in vivo. Male 6 week-old FVB/N mice received either streptozotocin (55 mg/kg/day i.p. for 5 days, n=17), to induce type 1 diabetes, or citrate vehicle (n=16). After 4 weeks of hyperglycemia, mice were allocated to 1-NCA therapy (83mg/kg/day i.p.) or vehicle, and followed for a further 4 weeks. As shown in the table, blood glucose was unaffected by 1-NCA. LV diastolic dysfunction was evident in diabetic mice, measured as echocardiography-derived A wave velocity, deceleration time and E:A ratio; LV systolic function was preserved. Diabetes-induced diastolic dysfunction was accompanied by increased LV cardiomyocyte size, hypertrophic and pro-fibrotic gene expression, and upregulation of LV superoxide. These characteristics of diabetic cardiomyopathy were largely prevented by 1-NCA treatment. Selectivity of 1-NCA as a donor of HNO versus NO• was demonstrated by the sensitivity of the coronary vasodilation response of 1-NCA to the HNO scavenger L-cysteine (4mM), but not to the NO• scavenger hydroxocobalamin (50μM), in the normal rat heart ex vivo (n=3-7). Collectively, our studies provide the first evidence that HNO donors may represent a promising new strategy for the treatment of diabetic cardiomyopathy, and implies their therapeutic efficacy in settings of chronic heart failure.

scholarly journals Glial Hedgehog and lipid metabolism regulate neural stem cell proliferation in Drosophila

2020 ◽  
Author(s):  
Qian Dong ◽  
Michael Zavortink ◽  
Francesca Froldi ◽  
Sofya Golenkina ◽  
Tammy Lam ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Cell Cycle Progression ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
Post Translational Modification ◽  
Final Size ◽  
Neural Lineage ◽  
Signalling Molecule ◽  
Lipid Metabolism Genes ◽  
And Function

AbstractThe final size and function of the adult central nervous system (CNS) is determined by neuronal lineages generated by neural stem cells (NSCs) in the developing brain. In Drosophila, NSCs called neuroblasts (NBs) reside within a specialised microenvironment called the glial niche. Here, we explore non-autonomous glial regulation of NB proliferation. We show that lipid droplets (LDs) which reside within the glial niche are closely associated with the signalling molecule Hedgehog (Hh). Under physiological conditions, cortex glial Hh is autonomously required to sustain niche chamber formation, and non-autonomously restrained to prevent ectopic Hh signalling in the NBs. In the context of cortex glial overgrowth, induced by Fibroblast Growth Factor (FGF) activation, Hh and lipid storage regulators Lsd-2 and Fasn1 were upregulated, resulting in activation of Hh signalling in the NBs; which in turn disrupted NB cell cycle progression and reduced neuronal production. We show that the LD regulator Lsd-2 modulates Hh’s ability to signal to NBs, and de novo lipogenesis gene Fasn1 regulates Hh post-translational modification via palmitoylation. Together, our data suggest that the glial niche non-autonomously regulates NB proliferation and neural lineage size via Hh signaling that is modulated by lipid metabolism genes.

scholarly journals MiR-21 protected against diabetic cardiomyopathy induced diastolic dysfunction by targeting gelsolin

2018 ◽  
Vol 17 (1) ◽  
Author(s):  
Beibei Dai ◽  
Huaping Li ◽  
Jiahui Fan ◽  
Yanru Zhao ◽  
Zhongwei Yin ◽  
...  
Keyword(s):  
Diastolic Dysfunction ◽  
Diabetic Cardiomyopathy
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