scholarly journals Free fatty acid-induced muscle insulin resistance and glucose uptake dysfunction: Evidence for PKC activation and oxidative stress-activated signaling pathways

2009 ◽  
Vol 389 (2) ◽  
pp. 211-216 ◽  
Author(s):  
Rafik Ragheb ◽  
Gamila M.L. Shanab ◽  
Amina M. Medhat ◽  
Dina M. Seoudi ◽  
K. Adeli ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Glucose Uptake ◽  
Signaling Pathways ◽  
Muscle Insulin Resistance ◽  
Pkc Activation ◽  
And Oxidative Stress

Abstract 357: Hepatic ERK2 Suppresses Endoplasmic Reticulum Stress, Leading to Protection from Oxidative Stress and Endothelial Dysfunction

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Takehiko Kujiraoka ◽  
Yasushi Satoh ◽  
Makoto Ayaori ◽  
Yasunaga Shiraishi ◽  
Yuko Arai-Nakaya ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Endoplasmic Reticulum ◽  
Fatty Acid ◽  
Endothelial Dysfunction ◽  
Er Stress ◽  
Vascular Complications ◽  
Metabolic Remodeling ◽  
And Oxidative Stress

Background Insulin signaling comprises 2 major cascades, the IRS/PI3K/Akt and Ras/Raf/MEK/ERK pathways. Many studies on the tissue-specific effects of the former pathway had been conducted, however, the role of the latter cascade in tissue-specific insulin resistance had not been investigated. High glucose/fatty acid toxicity, inflammation and oxidative stress, all of which are associated with insulin resistance, can activate ERK. Liver plays a central role of metabolism and hepatosteatosis (HST) is associated with vascular diseases. The aim of this study is to elucidate the role of hepatic ERK2 in HST, metabolic remodeling and endothelial dysfunction. Methods Serum biomarkers of vascular complications in human were compared between subjects with and without HST diagnosed by echography for regular medical checkup. Next, we created liver-specific ERK2 knockout mice (LE2KO) and fed them with a high-fat/high-sucrose diet (HFHSD) for 20 weeks. The histological analysis, the expression of hepatic sarco/endoplasmic reticulum (ER) Ca 2+ -ATPase 2 (SERCA2) and glucose-tolerance/insulin-sensitivity (GT/IS) were tested. Vascular superoxide production and endothelial function were evaluated with dihydroethidium staining and isometric tension measurement of aorta. Results The presence of HST significantly increased HOMA-IR, an indicator of insulin resistance or atherosclerotic index in human. HFHSD-fed LE2KO revealed a marked exacerbation in HST and metabolic remodeling represented by the impairment of GT/IS, elevated serum free fatty acid and hyperhomocysteinemia without changes in body weight, blood pressure and serum cholesterol/triglyceride levels. In the HFHSD-fed LE2KO, mRNA and protein expressions of hepatic SERCA2 were significantly decreased, which resulted in hepatic ER stress. Induction of vascular superoxide production and remarkable endothelial dysfunction were also observed in them. Conclusions Hepatic ERK2 revealed the suppression of hepatic ER stress and HST in vivo , which resulted in protection from vascular oxidative stress and endothelial dysfunction. HST with hepatic ER stress can be a prominent risk of vascular complications by metabolic remodeling and oxidative stress in obese-related diseases.

scholarly journals Dietaryα-lactalbumin induced fatty liver by enhancing nuclear liver X receptorαβ/sterol regulatory element-binding protein-1c/PPARγexpression and minimising PPARα/carnitine palmitoyltransferase-1 expression and AMP-activated protein kinaseαphosphorylation associated with atherogenic dyslipidaemia, insulin resistance and oxidative stress in Balb/c mice

2017 ◽  
Vol 118 (11) ◽  
pp. 914-929 ◽  
Author(s):  
María Elvira López-Oliva ◽  
Alba Garcimartin ◽  
Emilia Muñoz-Martínez
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Fatty Acid ◽  
Regulatory Element ◽  
Liver Steatosis ◽  
Element Binding Protein ◽  
Atherogenic Dyslipidaemia ◽  
Sterol Regulatory Element ◽  
Carnitine Palmitoyltransferase 1 ◽  
And Oxidative Stress

AbstractThe effect and the role played by dietaryα-lactalbumin (α-LAC) on hepatic fat metabolism are yet to be fully elucidated. We reported previously thatα-LAC intake induced atherogenic dyslipidaemia in Balb/c mice. The aim of the present study was to investigate if this atherogenic effect could be due to a possibleα-LAC-induced hepatic steatosis. We examine the ability of dietaryα-LAC to induce liver steatosis, identifying the molecular mechanisms underlying hepatic lipid metabolism in association with the lipid profile, peripheral insulin resistance (IR) and changes in the hepatic oxidative environment. Male Balb/c mice (n6) were fed with diets containing either chow or 14 %α-LAC for 4 weeks. Theα-LAC-fed mice developed abdominal adiposity and IR. Moderate liver steatosis with increased TAG and NEFA contents was correlated with atherogenic dyslipidaemia. There was increased nuclear expression of liver X receptorαβ(LXRαβ), sterol regulatory element-binding protein-1c (SREBP-1c) and PPARγtranscription factors and of the cytosolic enzymes acetyl-CoA carboxylase 1 (ACC1) and fatty acid synthase involved in the hepaticde novolipogenesis. The opposite was found for the nuclear receptor PPARαand the mitochondrial enzyme carnitine palmitoyltransferase-1 (CPT-1), leading to reduced fatty acidβ-oxidation (FAO). These changes were associated with a significant decrease in both p-Thr172-AMP-activated protein kinaseα(AMPKα) (inactivation) and p-Ser79-ACC1 (activation) and with a more oxidative liver environment increasing lipid peroxidation and protein oxidation and reducing GSH:GSSG ratio in theα-LAC-fed mice. In conclusion, 4 weeks of 14 %α-LAC feeding induced liver steatosis associated with atherogenic dyslipidaemia, IR and oxidative stress by enhancing nuclear LXRαβ/SREBP-1c/PPARγexpression and diminishing PPARα/CPT-1 expression and AMPKαphosphorylation shifting the hepatic FAO toward fatty acid synthesis in Balb/c mice.

scholarly journals Effects of free fatty acid elevation on hepatic insulin resistance and hepatic oxidative stress

2009 ◽  
Vol 17 (23) ◽  
pp. 2405
Author(s):  
Yan Lu ◽  
Ping Han ◽  
Sheng Zhao ◽  
Yong-Yan Zhang ◽  
Bing He ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Hepatic Insulin Resistance ◽  
Hepatic Oxidative Stress

Skeletal muscle insulin resistance: role of inflammatory cytokines and reactive oxygen species

2008 ◽  
Vol 294 (3) ◽  
pp. R673-R680 ◽  
Author(s):  
Yongzhong Wei ◽  
Kemin Chen ◽  
Adam T. Whaley-Connell ◽  
Craig S. Stump ◽  
Jamal A. Ibdah ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Inflammatory Cytokines ◽  
Molecular Mechanisms ◽  
Low Grade ◽  
Muscle Insulin Resistance ◽  
Skeletal Muscle Insulin Resistance ◽  
Increased Risk ◽  
And Oxidative Stress

The cardiometabolic syndrome (CMS), with its increased risk for cardiovascular disease (CVD), nonalcoholic fatty liver disease (NAFLD), and chronic kidney disease (CKD), has become a growing worldwide health problem. Insulin resistance is a key factor for the development of the CMS and is strongly related to obesity, hyperlipidemia, hypertension, type 2 diabetes mellitus (T2DM), CKD, and NAFLD. Insulin resistance in skeletal muscle is particularly important since it is normally responsible for more than 75% of all insulin-mediated glucose disposal. However, the molecular mechanisms responsible for skeletal muscle insulin resistance remain poorly defined. Accumulating evidence indicates that low-grade chronic inflammation and oxidative stress play fundamental roles in the development of insulin resistance, and inflammatory cytokines likely contribute to the link between inflammation, oxidative stress, and skeletal muscle insulin resistance. Understanding the mechanisms by which skeletal muscle tissue develops resistance to insulin will provide attractive targets for interventions, which may ultimately curb this serious problem. This review is focused on the effects of inflammatory cytokines and oxidative stress on insulin signaling in skeletal muscle and consequent development of insulin resistance.

scholarly journals 18beta‐glycyrrhetinic acid prevents free fatty acid‐induced lipotoxicity by inhibiting ER stress and oxidative stress

2009 ◽  
Vol 23 (S1) ◽  
Author(s):  
Xudong Wu ◽  
Weibin Zha ◽  
Lixin Sun ◽  
Beth S Pecora ◽  
Risheng Cao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Er Stress ◽  
Glycyrrhetinic Acid ◽  
And Oxidative Stress

scholarly journals Skeletal Muscle Insulin Resistance: Roles of Fatty Acid Metabolism and Exercise

2008 ◽  
Vol 88 (11) ◽  
pp. 1279-1296 ◽  
Author(s):  
Lorraine P Turcotte ◽  
Jonathan S Fisher
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Fatty Acid ◽  
Exercise Training ◽  
Aerobic Exercise ◽  
Glucose Uptake ◽  
Muscle Cells ◽  
Aerobic Exercise Training ◽  
Muscle Insulin Resistance ◽  
Skeletal Muscle Insulin Resistance

The purpose of this review is to provide information about the role of exercise in the prevention of skeletal muscle insulin resistance, that is, the inability of insulin to properly cause glucose uptake into skeletal muscle. Insulin resistance is associated with high levels of stored lipids in skeletal muscle cells. Aerobic exercise training decreases the amounts of these lipid products and increases the lipid oxidative capacity of muscle cells. Thus, aerobic exercise training may prevent insulin resistance by correcting a mismatch between fatty acid uptake and fatty acid oxidation in skeletal muscle. Additionally, a single session of aerobic exercise increases glucose uptake by muscle during exercise, increases the ability of insulin to promote glucose uptake, and increases glycogen accumulation after exercise, all of which are important to blood glucose control. There also is some indication that resistance exercise may be effective in preventing insulin resistance. The information provided is intended to help clinicians understand and explain the roles of exercise in reducing insulin resistance.

Abstract 326: Cd36 Deficiency Reduces Obesity-associated Inflammation And Oxidative Stress In Heart

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Tahar Hajri ◽  
Mohamed Gharib ◽  
Thomas V Fungwe
Keyword(s):  
Oxidative Stress ◽  
Fatty Acid ◽  
Glucose Uptake ◽  
Fatty Acid Oxidation ◽  
P38 Mapk ◽  
Acid Oxidation ◽  
Cd36 Deficiency ◽  
Anti Oxidant ◽  
The Impact ◽  
And Oxidative Stress

OBJECTIVE: Obesity is often associated with diabetes and cardiovascular diseases (CVD). Mounting evidence shows that diabetes is associated with structural and functional changes in the heart. CD36 protein is highly expressed in heart and regulates lipid utilization in cardiacmyocytes. In this paper, we investigated the impact of CD36 expression on obesity-associated inflammation and oxidative stress in heart. METHODS: Studies were conducted in control lean (WT), obese leptin deficient (Lep Ob/Ob ) and leptin deficient-CD36 null (Lep Ob/Ob -CD36 -/- ) mice. To examine obesity-associated insulin resistance, glucose uptake and insulin signaling were examined in adult mouse hearts. Presence of macrophages in heart was examined with immunohistochemisty. Oxidative stress makers and activity of anti-oxidant enzymes were measured in hearts. To evaluate substrate utilization, glucose and fatty acid oxidation was tested in primary cultures of ventricular myocytes. Finally, the activity of pro-inflammatory kinases p38 mitogen-activated protein kinases (p38-MAPK), c-Jun NH2-terminal kinases (JNK) were examined in cardiacmyocytes challenged with palmitate. RESULTS: In Lep Ob/Ob , glucose uptake and oxidation in heart was lower than lean WT mice, while cardiac FA oxidation was strongly higher. Silencing CD36 in Lep Ob/Ob mouse markedly improved insulin sensitivity and glucose uptake in heart, but resulted in marked reduction of FA oxidation. Immunostaining of heart sections with macrophage specific antibody F4/80 showed that macrophage content was higher in myocardium of Lep Ob/Ob mice than Lep Ob/Ob -CD36 -/- mice. Moreover, oxidative stress markers, isoprostanes and reactive oxygen species, and expression of pro-inflammatory cytokines were higher in hearts of Lep Ob/Ob than Lep Ob/Ob -CD36-/- mice, although the activities of anti-oxidant enzymes were comparable. Chronic overload of Lep Ob/Ob cardiac myocyte with palmitate strongly induced the activity of JNK and p38-MAPK, but was less effective in Lep Ob/Ob -CD36 -/- cardiac myocytes. CONCLUSIONS: These results show that CD36 deficiency induced a significant reduction of obesity-associated oxidative stress and inflammation in heart in parallel to a drop in fatty acid oxidation.

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