scholarly journals Rescue of cardiac leptin receptors in db/db mice prevents myocardial triglyceride accumulation

2014 ◽  
Vol 307 (3) ◽  
pp. E316-E325 ◽  
Author(s):  
Michael E. Hall ◽  
Matthew W. Maready ◽  
John E. Hall ◽  
David E. Stec
Keyword(s):  
Body Weight ◽  
Lipid Accumulation ◽  
Leptin Receptor ◽  
Systolic Function ◽  
Left Ventricular ◽  
Diastolic Filling ◽  
Cardiac Lipid ◽  
Leptin Receptors ◽  
Triglyceride Accumulation ◽  
Long Form

Increased leptin levels have been suggested to contribute to cardiac hypertrophy and attenuate cardiac lipid accumulation in obesity, although it has been difficult to separate leptin's direct effects from those caused by changes in body weight and adiposity. To determine whether leptin attenuates cardiac lipid accumulation in obesity or directly causes left ventricular hypertrophy (LVH), we generated a novel mouse model in which the long form of the leptin receptor (LepR) was “rescued” only in cardiomyocytes of obese db/db mice. Reexpression of cardiomyocyte leptin receptors in db/db mice did not cause LVH but reduced cardiac triglycerides and improved cardiac function. Compared with lean wild-type (WT) or db/db-cardiac LepR rescue mice, db/db mice exhibited significantly lower E/A ratio, a measurement of early to late diastolic filling, which averaged 1.5 ± 0.07 in db/db vs. 1.9 ± 0.08 and 1.8 ± 0.11 in WT and db/db-cardiac LepR rescue mice, respectively. No differences in systolic function were observed. Although db/db and db/db-cardiac LepR rescue mice exhibited similar increases in plasma triglycerides, insulin, glucose, and body weight, cardiac triglycerides were significantly higher in db/db compared with WT and db/db cardiac LepR rescue mice, averaging 13.4 ± 4.2 vs. 3.8 ± 1.6 vs. 3.8 ± 0.7 mg/g, respectively. These results demonstrate that despite significant obesity and increases in plasma glucose and triglycerides, db/db cardiac LepR rescue mice are protected against myocardial lipid accumulation. However, we found no evidence that leptin directly causes LVH.

scholarly journals Cardiomyocyte-specific deletion of leptin receptors causes lethal heart failure in Cre-recombinase-mediated cardiotoxicity

2012 ◽  
Vol 303 (12) ◽  
pp. R1241-R1250 ◽  
Author(s):  
Michael E. Hall ◽  
Grant Smith ◽  
John E. Hall ◽  
David E. Stec
Keyword(s):  
Heart Failure ◽  
Cardiac Function ◽  
Leptin Receptor ◽  
Systolic Function ◽  
Mammalian Target Of Rapamycin ◽  
Left Ventricular Systolic Function ◽  
Cre Recombinase ◽  
Left Ventricular ◽  
Leptin Receptors ◽  
Specific Deletion

Although disruption of leptin signaling is associated with obesity as well as cardiac lipid accumulation and dysfunction, it has been difficult to separate the direct effects of leptin on the heart from those associated with the effects of leptin on body weight and fat mass. Using Cre-loxP recombinase technology, we developed tamoxifen-inducible, cardiomyocyte-specific leptin receptor-deficient mice to assess the role of leptin in regulating cardiac function. Cre recombinase activation in the heart resulted in transient reduction in left ventricular systolic function which recovered to normal levels by day 10. However, when cardiomyocyte leptin receptors were deleted in the setting of Cre recombinase-induced left ventricular dysfunction, irreversible lethal heart failure was observed in less than 10 days in all mice. Heart failure after leptin receptor deletion was associated with marked decreases of cardiac mitochondrial ATP, phosphorylated mammalian target of rapamycin (mTOR), and AMP-activated kinase (pAMPK). Our results demonstrate that specific deletion of cardiomyocyte leptin receptors, in the presence of increased Cre recombinase expression, causes lethal heart failure associated with decreased cardiac energy production. These observations indicate that leptin plays an important role in regulating cardiac function in the setting of cardiac stress caused by Cre-recombinase expression, likely through actions on cardiomyocyte energy metabolism.

Hyperleptinemia and reduced TNF-α secretion cause resistance of db/db mice to endotoxin

2003 ◽  
Vol 284 (3) ◽  
pp. R763-R770 ◽  
Author(s):  
Abram M. Madiehe ◽  
Tiffany D. Mitchell ◽  
Ruth B. S. Harris
Keyword(s):  
Rectal Temperature ◽  
Leptin Receptor ◽  
Short Form ◽  
Endotoxic Shock ◽  
Cytokine Receptors ◽  
Leptin Receptors ◽  
Leptin Deficiency ◽  
Tnf Α ◽  
Long Form

Leptin deficiency in ob/ob mice increases susceptibility to endotoxic shock, whereas leptin pretreatment protects them against LPS-induced lethality. Lack of the long-form leptin receptor (Ob-Rb) in db/db mice causes resistance. We tested the effects of LPS in C57BL/6J db3J/db3J (BL/3J) mice, which express only the circulating leptin receptors, compared with C57BL/6J db/db (BL/6J) mice, which express all short-form and circulating isoforms of the leptin receptor. Intraperitoneal injections of LPS significantly decreased rectal temperature and increased leptin, corticosterone, and free TNF-α in fed and fasted BL/3J and BL/6J mice. TNF-α was increased three- and fourfold in BL/3J and BL/6J, respectively. LPS (100 μg) caused 50% mortality of fasted BL/6J mice but caused no mortality in fasted BL/3J mice. Pretreatment of fasted BL/3J mice with 30 μg leptin prevented the drop in rectal temperature, blunted the increase in corticosterone, but had no effect on TNF-α induced by 100 μg LPS. Taken together, these data provide evidence that fasted BL/3J mice are more resistant than BL/6J mice to LPS toxicity, presumably due to the absence of leptin receptors in BL/3J mice. This resistance may be due to high levels of free leptin cross-reacting with other cytokine receptors.

scholarly journals Decreased Expression of Natriuretic Peptides Associated with Lipid Accumulation in Cardiac Ventricle of Obese Mice

2010 ◽  
Vol 31 (5) ◽  
pp. 775-775
Author(s):  
Emil Daniel Bartels ◽  
Jan Møller Nielsen ◽  
Line Stattau Bisgaard ◽  
Jens P. Goetze ◽  
Lars Bo Nielsen
Keyword(s):  
Cardiac Function ◽  
Natriuretic Peptide ◽  
Mouse Models ◽  
Natriuretic Peptides ◽  
Lipid Accumulation ◽  
Cardiac Lipid ◽  
Triglyceride Accumulation ◽  
Cardiac Ventricle ◽  
The Impact ◽  
Impaired Cardiac Function

Plasma B-type natriuretic peptide (BNP) and proBNP are established markers of cardiac dysfunction. Even though obesity increases the risk of cardiovascular disease, obese individuals have reduced plasma concentrations of natriuretic peptides. The underlying mechanism is not established. We used cultured cardiomyocytes and three different mouse models to examine the impact of obesity and cardiac lipid accumulation on cardiac natriuretic peptide expression. The cardiac ventricular expression of atrial natriuretic peptide (ANP) and BNP mRNA and ANP peptide was decreased 36-72% in obese ob/ob, db/db, and fat-fed C57BL/6 mice as compared with their respective controls. The db/db and ob/ob mice displayed impaired cardiac function, whereas the fat-fed mice had almost normal cardiac function. Moreover, the ventricular expression of hypertrophic genes (α- and β-major histocompatibility complex and α-actin) and natriuretic peptide receptor genes were not consistently altered by obesity across the three mouse models. In contrast, cardiac ventricular triglycerides were similarly increased by 60-115% in all three obese mouse models and incubation with oleic acid caused triglyceride accumulation and an approximately 35% (P < 0.005) depression of ANP mRNA expression in cultured HL-1 atrial myocytes. The data suggest that obesity and altered cardiac lipid metabolism are associated with reduced production of ANP and BNP in the cardiac ventricles in the setting of normal as well as impaired cardiac function.

scholarly journals Non-invasive intraventricular pressure differences estimated with cardiac MRI in subjects without heart failure and with heart failure with reduced and preserved ejection fraction

Open Heart ◽  
2019 ◽  
Vol 6 (2) ◽  
pp. e001088 ◽  
Author(s):  
Francisco Londono-Hoyos ◽  
Patrick Segers ◽  
Zeba Hashmath ◽  
Garrett Oldland ◽  
Maheshwara Reddy Koppula ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Systolic Function ◽  
Left Ventricular ◽  
Diastolic Filling ◽  
Spatiotemporal Pattern ◽  
Intraventricular Pressure ◽  
Preserved Ejection Fraction ◽  
Non Invasive ◽  
Echocardiographic Parameters

ObjectiveNon-invasive assessment of left ventricular (LV) diastolic and systolic function is important to better understand physiological abnormalities in heart failure (HF). The spatiotemporal pattern of LV blood flow velocities during systole and diastole can be used to estimate intraventricular pressure differences (IVPDs). We aimed to demonstrate the feasibility of an MRI-based method to calculate systolic and diastolic IVPDs in subjects without heart failure (No-HF), and with HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF).MethodsWe studied 159 subjects without HF, 47 subjects with HFrEF and 32 subjects with HFpEF. Diastolic and systolic intraventricular flow was measured using two-dimensional in-plane phase-contrast MRI. The Euler equation was solved to compute IVPDs in diastole (mitral base to apex) and systole (apex to LV outflow tract).ResultsSubjects with HFpEF demonstrated a higher magnitude of the early diastolic reversal of IVPDs (−1.30 mm Hg) compared with the No-HF group (−0.78 mm Hg) and the HFrEF group (−0.75 mm Hg; analysis of variance p=0.01). These differences persisted after adjustment for clinical variables, Doppler-echocardiographic parameters of diastolic filling and measures of LV structure (No-HF=−0.72; HFrEF=−0.87; HFpEF=−1.52 mm Hg; p=0.006). No significant differences in systolic IVPDs were found in adjusted models. IVPD parameters demonstrated only weak correlations with standard Doppler-echocardiographic parameters.ConclusionsOur findings suggest distinct patterns of systolic and diastolic IVPDs in HFpEF and HFrEF, implying differences in the nature of diastolic dysfunction between the HF subtypes.

Evaluation of Cardiac Scan in Diagnosing Coronary-artery Disease

2020 ◽  
Vol 16 (8) ◽  
pp. 1022-1028
Author(s):  
Zubaida Butaish ◽  
Masheal Alajmi ◽  
Arouba Elahi ◽  
Saeed M. Bafaraj
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Systolic Function ◽  
Imaging Techniques ◽  
Cost Effective ◽  
Left Ventricular ◽  
Diastolic Filling ◽  
Study Results ◽  
Artery Disease ◽  
Lv Systolic Function

Background: With the evaluation of focal epicardial coronary stenosis and non-obstructive atherosclerosis, the cardiac scans play a significant role in diagnosing coronary artery disease (CAD). Moreover, the advancements in the imaging techniques leading to improved risk assessment and timely therapies help in early diagnosis of CAD with greater accuracy. Aims: To evaluate the role of cardiac scan in diagnosing CAD. Methods: Recruited 100 individuals without any history of CAD that refers to the assessment of suspected angina, conducted the prospective study. Electrocardiogram (ECG) findings assisted in the evaluation of left bundle branch blockage, abnormalities of ST-segment, and pathological Q waves. Results: The results depicted negative N.M findings among 38 respondents; whereas, ischemia and myocardial infarctions were diagnosed in 26% and 19% of the respondents, respectively. The majority of the males (59) were positive in contrast to 37 females with positive results. Similarly, 24 respondents were presented with mild dilated left atria (LA), 37 respondents suffered from impaired relaxation pattern of left ventricular (LV) diastolic filling; while, 40 of the respondents had normal global LV systolic function. Conclusion: The study results have concluded that non-invasive, low-risk, and cost-effective technique like ECG is an important beneficial advancement in the diagnosis of CAD.

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