scholarly journals Genetic Ablation of Calcium-independent Phospholipase A2γ Prevents Obesity and Insulin Resistance during High Fat Feeding by Mitochondrial Uncoupling and Increased Adipocyte Fatty Acid Oxidation

2010 ◽  
Vol 285 (47) ◽  
pp. 36495-36510 ◽  
Author(s):  
David J. Mancuso ◽  
Harold F. Sims ◽  
Kui Yang ◽  
Michael A. Kiebish ◽  
Xiong Su ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Acid Oxidation ◽  
High Fat ◽  
Mitochondrial Uncoupling ◽  
Genetic Ablation ◽  
Fat Feeding

scholarly journals Peroxisome Proliferator-Activated Receptor α Mediates the Effects of High-Fat Diet on Hepatic Gene Expression

Endocrinology ◽  
2006 ◽  
Vol 147 (3) ◽  
pp. 1508-1516 ◽  
Author(s):  
David Patsouris ◽  
Janardan K. Reddy ◽  
Michael Müller ◽  
Sander Kersten
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Microarray Analysis ◽  
High Fat Diet ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Wild Type ◽  
High Fat ◽  
Fat Feeding

Peroxisome proliferator-activated receptors (PPARs) are transcription factors involved in the regulation of numerous metabolic processes. The PPARα isotype is abundant in liver and activated by fasting. However, it is not very clear what other nutritional conditions activate PPARα. To examine whether PPARα mediates the effects of chronic high-fat feeding, wild-type and PPARα null mice were fed a low-fat diet (LFD) or high-fat diet (HFD) for 26 wk. HFD and PPARα deletion independently increased liver triglycerides. Furthermore, in wild-type mice HFD was associated with a significant increase in hepatic PPARα mRNA and plasma free fatty acids, leading to a PPARα-dependent increase in expression of PPARα marker genes CYP4A10 and CYP4A14. Microarray analysis revealed that HFD increased hepatic expression of characteristic PPARα target genes involved in fatty acid oxidation in a PPARα-dependent manner, although to a lesser extent than fasting or Wy14643. Microarray analysis also indicated functional compensation for PPARα in PPARα null mice. Remarkably, in PPARα null mice on HFD, PPARγ mRNA was 20-fold elevated compared with wild-type mice fed a LFD, reaching expression levels of PPARα in normal mice. Adenoviral overexpression of PPARγ in liver indicated that PPARγ can up-regulate genes involved in lipo/adipogenesis but also characteristic PPARα targets involved in fatty acid oxidation. It is concluded that 1) PPARα and PPARα-signaling are activated in liver by chronic high-fat feeding; and 2) PPARγ may compensate for PPARα in PPARα null mice on HFD.

Differential effects of high-fat diet on myocardial lipid metabolism in failing and nonfailing hearts with angiotensin II-mediated cardiac remodeling in mice

2012 ◽  
Vol 302 (9) ◽  
pp. H1795-H1805 ◽  
Author(s):  
Corinne Pellieux ◽  
Christophe Montessuit ◽  
Irène Papageorgiou ◽  
Thierry Pedrazzini ◽  
René Lerch
Keyword(s):  
Heart Failure ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
High Fat Diet ◽  
Regulatory Proteins ◽  
Acid Oxidation ◽  
Contractile Dysfunction ◽  
High Fat ◽  
Palmitate Oxidation ◽  
Fat Feeding

Normal myocardium adapts to increase of nutritional fatty acid supply by upregulation of regulatory proteins of the fatty acid oxidation pathway. Because advanced heart failure is associated with reduction of regulatory proteins of fatty acid oxidation, we hypothesized that failing myocardium may not be able to adapt to increased fatty acid intake and therefore undergo lipid accumulation, potentially aggravating myocardial dysfunction. We determined the effect of high-fat diet in transgenic mice with overexpression of angiotensinogen in the myocardium (TG1306/R1). TG1306/R1 mice develop ANG II-mediated left ventricular hypertrophy, and at one year of age approximately half of the mice present heart failure associated with reduced expression of regulatory proteins of fatty acid oxidation and reduced palmitate oxidation during ex vivo working heart perfusion. Hypertrophied hearts from TG1306/R1 mice without heart failure adapted to high-fat feeding, similarly to hearts from wild-type mice, with upregulation of regulatory proteins of fatty acid oxidation and enhancement of palmitate oxidation. There was no myocardial lipid accumulation or contractile dysfunction. In contrast, hearts from TG1306/R1 mice presenting heart failure were unable to respond to high-fat feeding by upregulation of fatty acid oxidation proteins and enhancement of palmitate oxidation. This resulted in accumulation of triglycerides and ceramide in the myocardium, and aggravation of contractile dysfunction. In conclusion, hearts with ANG II-induced contractile failure have lost the ability to enhance fatty acid oxidation in response to increased fatty acid supply. The ensuing accumulation of lipid compounds may play a role in the observed aggravation of contractile dysfunction.

scholarly journals Consumption of a Mango Fruit Powder Protects Mice from High-Fat Induced Insulin Resistance and Hepatic Fat Accumulation

2017 ◽  
Vol 42 (2) ◽  
pp. 564-578 ◽  
Author(s):  
Agustín G. Sabater ◽  
Joan Ribot ◽  
Teresa Priego ◽  
Itxaso Vazquez ◽  
Sonja Frank ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acid ◽  
Insulin Sensitivity ◽  
Fatty Acid Oxidation ◽  
High Fat Diet ◽  
Acid Oxidation ◽  
High Fat ◽  
Food Ingredient ◽  
Mango Fruit ◽  
Fruit Powder

Background/Aims: The aim of this study was to gain more insight into the beneficial effects of mango fruit powder on the early metabolic adverse effects of a high-fat diet. Methods: The progressive dose-response effects of mango fruit powder on body composition, circulating parameters, and the expression of genes related to fatty acid oxidation and insulin sensitivity in key tissues were studied in mice fed a moderate (45%) high-fat diet. Results: Findings suggest that mango fruit powder exerts physiological protective effects in the initial steps of insulin resistance and hepatic lipid accumulation induced by a high-fat diet in mice. Moreover, AMPK and SIRT1 appear as key regulators of the observed improvement in fatty acid oxidation capacity, as well as of the improved insulin sensitivity and the increased glucose uptake and metabolism through the glycolytic pathway capacity in liver and skeletal muscle. Conclusion: In summary, this study provides evidence that the functional food ingredient (CarelessTM) from mango fruit prevents early metabolic alterations caused by a high-fat diet in the initial stages of the metabolic syndrome.

Regulation of cardiac and skeletal muscle malonyl-CoA decarboxylase by fatty acids

2001 ◽  
Vol 280 (3) ◽  
pp. E471-E479 ◽  
Author(s):  
Martin E. Young ◽  
Gary W. Goodwin ◽  
Jun Ying ◽  
Patrick Guthrie ◽  
Christopher R. Wilson ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Rat Heart ◽  
Acid Oxidation ◽  
High Fat ◽  
Nonesterified Fatty Acids ◽  
Malonyl Coa ◽  
Fat Feeding

Malonyl-CoA decarboxylase (MCD) catalyzes the degradation of malonyl-CoA, an important modulator of fatty acid oxidation. We hypothesized that increased fatty acid availability would increase the expression and activity of heart and skeletal muscle MCD, thereby promoting fatty acid utilization. The results show that high-fat feeding, fasting, and streptozotocin-induced diabetes all significantly increased the plasma concentration of nonesterified fatty acids, with a concomitant increase in both rat heart and skeletal muscle MCD mRNA. Upon refeeding of fasted animals, MCD expression returned to basal levels. Fatty acids are known to activate peroxisome proliferator-activated receptor-α (PPARα). Specific PPARα stimulation, through Wy-14643 treatment, significantly increased the expression of MCD in heart and skeletal muscle. Troglitazone, a specific PPARγ agonist, decreased MCD expression. The sensitivity of MCD induction by fatty acids and Wy-14643 was soleus > extensor digitorum longus > heart. High plasma fatty acids consistently increased MCD activity only in solei, whereas MCD activity in the heart actually decreased with high-fat feeding. Pressure overload-induced cardiac hypertrophy, in which PPARα expression is decreased (and fatty acid oxidation is decreased), resulted in decreased MCD mRNA and activity, an effect that was dependent on fatty acids. The results suggest that fatty acids induce the expression of MCD in rat heart and skeletal muscle. Additional posttranscriptional mechanisms regulating MCD activity appear to exist.

scholarly journals MicroRNA-27b-3p regulates function and metabolism in insulin resistance cells by inhibiting receptor tyrosine kinase-like orphan receptor 1

2018 ◽  
Vol 16 ◽  
pp. 205873921876205
Author(s):  
Yong Liu ◽  
Guohui Wang ◽  
Xiangwu Yang ◽  
Pengzhou Li ◽  
Hao Ling ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acid ◽  
Tyrosine Kinase ◽  
Glucose Uptake ◽  
Fatty Acid Oxidation ◽  
Receptor Tyrosine Kinase ◽  
Cell Model ◽  
Orphan Receptor ◽  
Acid Oxidation ◽  
Metabolism Disorder

Type 2 diabetes mellitus (T2DM) is associated with insulin resistance-induced lipid and glucose metabolism disorder. The study was aimed to explore the potential functional role of microRNA (miR)-27b-3p in T2DM, as well as underlying mechanisms. An insulin resistance cell model was induced in HepG2 cells and then expression of miR-27b-3p and receptor tyrosine kinase-like orphan receptor 1 (ROR1) was analyzed. The expression of miR-27b-3p was overexpressed or silenced, and the relationship between ROR1 and miR-27b-3p was investigated. Thereafter, the effects of miR-27b-3p on percentage of glucose uptake, fatty acid oxidation and cell cycle were analyzed. The expressions of miR-27b-3p were significantly increased, while the ROR1 levels were statistically decreased in the cells of the model group. Overexpression of miR-27b-3p dramatically decreased the levels of ROR1 and the percentage of glucose uptake, but had no effects on fatty acid oxidation. ROR1 was a target of miR-27b-3p. Moreover, overexpression of miR-27b-3p could remarkably highlight the percentages of cells at G0/G1 phase, but decreased the percentages of cells at S phase. In conclusion, our results suggest that miR-27b-3p regulates the function and metabolism of insulin resistance cells by inhibiting ROR1. miR-27b-3p might be a potential drug target in treating T2DM.

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.

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