Abstract 122: Hyperinsulinmia Promotes Cardiac Dysfunction via Upregulation of Phosphodiesterase in Heart

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Yang K Xiang
Keyword(s):  
Insulin Signaling ◽  
Cardiac Dysfunction ◽  
High Fat Diet ◽  
Erk Pathway ◽  
High Fat ◽  
Heart Dysfunction ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Attractive Therapeutic Target ◽  
Phosphodiesterase 4D

Accumulating evidence suggests that hyperinsulinemia contributes to heart dysfunction. Here we show that insulin signaling is responsible for high fat diet (HFD) feeding-induced expression of phosphodiesterase 4D (PDE4D) in the myocardium of mice. The increased expression of PDE4D, in concert with reduced phosphorylation of phospholamban (PLB), promotes systolic and diastolic heart dysfunction. We revealed that insulin-mediated induction of PDE4D was dependent on β2AR-mediaed β-arrestin2-ERK pathway, which is transactivated in a GRK2-dependent fashion. Deletion of β2AR gene significantly attenuated insulin-induced phosphorylation of extracellular signal-regulated kinase (ERK) and Akt, as well as the upregulation of PDE4D expression, which prevented the heart dysfunction. β-arrestin2 KO mice did not display increased PDE4D expression and did not develop systolic or diastolic dysfunction following HFD. In brief, these data indicate that chronic hyperinsulinimia leads to heart dysfunction by increasing PDE4D expression via β2AR-GRK2-β-arrestin2 -ERK pathway, which suggests that β2AR signaling could be an attractive therapeutic target for preserving or improving cardiac function in subjects with insulin resistance.

scholarly journals Regular Intake of Pistachio Mitigates the Deleterious Effects of a High Fat-Diet in the Brain of Obese Mice

Antioxidants ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 317 ◽  
Author(s):  
Domenico Nuzzo ◽  
Giacoma Galizzi ◽  
Antonella Amato ◽  
Simona Terzo ◽  
Pasquale Picone ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Serum Levels ◽  
Standard Diet ◽  
High Fat ◽  
Neuroprotective Effects ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
The Brain ◽  
Superoxide Dismutase 2 ◽  
Regular Intake

Obesity has been associated with neurodegeneration and cognitive dysfunctions. Recent data showed that pistachio consumption is able to prevent and ameliorate dyslipidemia, hepatic steatosis, systemic and adipose tissue inflammation in mice fed a high-fat diet (HFD). The present study investigated the neuroprotective effects of pistachio intake in HFD mice. Three groups of mice were fed a standard diet (STD), HFD, or HFD supplemented with pistachio (HFD-P) for 16 weeks. Metabolic parameters (oxidative stress, apoptosis, and mitochondrial dysfunction) were analyzed by using specific assays and biomarkers. The pistachio diet significantly reduced the serum levels of triglycerides and cholesterol in the HFD model. No difference was observed in the index of insulin resistance between HFD and HFD-P. A higher number of fragmented nuclei were found in HFD cerebral cortex compared to STD and HFD-P. A decrease in reactive oxygen species, singlet oxygen and phosphorylated extracellular signal-regulated kinase, and an increase of superoxide dismutase 2 and heme oxygenase expression were found in the brains of the HFD-P samples compared to HFD. Furthermore, the impaired mitochondrial function found in HFD brain was partially recovered in HFD-P mice. These results suggest that the regular intake of pistachio may be useful in preventing obesity-related neurodegeneration, being able to reduce both metabolic and cellular dysfunctions.

Piperine, an LXRα antagonist, protects against hepatic steatosis and improves insulin signaling in mice fed a high-fat diet

2012 ◽  
Vol 84 (11) ◽  
pp. 1501-1510 ◽  
Author(s):  
Hyejeong Jwa ◽  
Youngshim Choi ◽  
Ui-Hyun Park ◽  
Soo-Jong Um ◽  
Seung Kew Yoon ◽  
...  
Keyword(s):  
Hepatic Steatosis ◽  
Insulin Signaling ◽  
High Fat Diet ◽  
High Fat

scholarly journals Maternal High‐Fat Diet Causes Cardiac Dysfunction and Increased Endotoxin Sensitivity in Offspring in Mice

2009 ◽  
Vol 23 (S1) ◽  
Author(s):  
Hong Huang ◽  
Hongyan Zhang ◽  
Brandon Schanbacher ◽  
Peter Giannone ◽  
John Bauer
Keyword(s):  
Cardiac Dysfunction ◽  
High Fat Diet ◽  
High Fat

scholarly journals Long‐Term Exposure of Obesity Induced by Unsaturated High‐Fat Diet promotes Cardiac Dysfunction and Increase of Myocardial Collagen

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Andre Leopoldo ◽  
Ana Paula Lima Leopoldo ◽  
Mário Sugizaki ◽  
André Nascimento ◽  
Dijon Campos ◽  
...  
Keyword(s):  
Cardiac Dysfunction ◽  
High Fat Diet ◽  
High Fat ◽  
Myocardial Collagen

Abstract 437: Increasing Cardiac Fatty Acid Oxidation Protects Against High Fat Diet Induced Cardiomyopathy in Mice

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Dan Shao ◽  
Nathan Roe ◽  
Loreta D Tomasi ◽  
Alyssa N Braun ◽  
Ana Mattos ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Cardiac Dysfunction ◽  
High Fat Diet ◽  
Heart Weight ◽  
Acid Oxidation ◽  
Acid Uptake ◽  
High Fat ◽  
Diet Induced Obesity ◽  
Cardiac Lipotoxicity

In the obese and diabetic heart, an imbalance between fatty acid uptake and fatty acid oxidation (FAO) promotes the development of cardiac lipotoxicity. We previously showed that cardiac specific deletion of acetyl CoA carboxylase 2 (ACC2) was effective in increasing myocardial FAO while maintaining normal cardiac function and energetics. In this study, we tested the hypothesis that ACC2 deletion in an adult heart would prevent the cardiac lipotoxic phenotype in a mouse model of diet-induced obesity. ACC2 flox/flox (CON) and ACC2 flox/flox-MerCreMer+ (iKO) after tamoxifen injection were subjected to a high fat diet (HFD) for 24 weeks. HFD induced similar body weight gain and glucose intolerance in CON and iKO. In isolated Langendorff-perfused heart experiments, HFD feeding increased FAO 1.6-fold in CON mice which was increased to 2.5-fold in iKO mice compared with CON on chow diet. Fractional shortening was significantly decreased in CON-HFD (32.8±2.8% vs. 39.2±3.2%, p< 0.05, n=5-6), but preserved in iKO-HFD mice (42.8±2.3%, vs. 38.5±1.4%, n=6), compared to respective chow fed controls. Diastolic function, assessed by E’/A’ ratio using tissue Doppler imaging, was significantly decreased in CON-HFD mice (1.11±0.08 vs. 0.91±0.09, p<0.05 n=5-6), while no difference was observed in iKO-HFD compared to iKO-chow (1.10±0.03 vs. 1.09±0.04, n=6). Heart weight /Tibia length ratio was significantly higher in CON than iKO mice after HFD feeding (7.19±0.22 vs. 6.47±0.28, p<0.05, n=6). Furthermore, HFD induced mitochondria super complex II, III and V instability, which was attenuated in iKO-HFD mice. These data indicate that elevated myocardial FAO per se does not cause the development of cardiac dysfunction in obese animals. In fact, enhancing FAO via ACC2 deletion prevents HFD induced cardiac dysfunction and attenuates pathological hypertrophy. These effects may be mediated, in part, by maintenance of mitochondrial integrity. Taken together, our findings suggest that promoting cardiac FAO is an effective strategy to resist the development of cardiac lipotoxicity during diet-induced obesity.

scholarly journals Analgesic Efficacy of a Combination of Fentanyl and a Japanese Herbal Medicine “Yokukansan” in Rats with Acute Inflammatory Pain

Medicines ◽  
2020 ◽  
Vol 7 (12) ◽  
pp. 75
Author(s):  
Yuko Akanuma ◽  
Mami Kato ◽  
Yasunori Takayama ◽  
Hideshi Ikemoto ◽  
Naoki Adachi ◽  
...  
Keyword(s):  
Inflammatory Pain ◽  
Late Phase ◽  
Analgesic Efficacy ◽  
Opioid Tolerance ◽  
High Dose ◽  
Erk Pathway ◽  
Single High Dose ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Combined Use

Background: Fentanyl can induce acute opioid tolerance and postoperative hyperalgesia when administered at a single high dose; thus, this study examined the analgesic efficacy of a combination of fentanyl and Yokukansan (YKS). Methods: Rats were divided into control, formalin-injected (FOR), YKS-treated+FOR (YKS), fentanyl-treated+FOR (FEN), and YKS+FEN+FOR (YKS+FEN) groups. Acute pain was induced via subcutaneous injection of formalin into the paw. The time engaged in pain-related behavior was measured. Results: In the early (0–10 min) and intermediate (10–20 min) phases, pain-related behavior in the YKS+FEN group was significantly inhibited compared with the FOR group. In the late phase (20–60 min), pain-related behavior in the FEN group was the longest and significantly increased compared with the YKS group. We explored the influence on the extracellular signal-regulated kinase (ERK) pathway in the spinal cord, and YKS suppressed the phosphorylated ERK expression, which may be related to the analgesic effect of YKS in the late phase. Conclusions: These findings suggest that YKS could reduce the use of fentanyl and combined use of YKS and fentanyl is considered clinically useful.

Ethno-pharmacological insulin signaling induction of aqueous extract of Syzygium paniculatum fruits in a high-fat diet induced hepatic insulin resistance

2020 ◽  
pp. 113576
Author(s):  
Prabhakar Yellanur Konda ◽  
Vidyasagar Chennupati ◽  
Sreenivasulu Dasari ◽  
Nishesh Sharma ◽  
Muthukumaran Muthulingam ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Aqueous Extract ◽  
Insulin Signaling ◽  
High Fat Diet ◽  
Hepatic Insulin Resistance ◽  
High Fat
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