scholarly journals Rapid Loss of Adiponectin-Stimulated Fatty Acid Oxidation in Skeletal Muscle of Rats Fed a High Fat Diet Is Not Due to Altered Muscle Redox State

PLoS ONE ◽  
2012 ◽  
Vol 7 (12) ◽  
pp. e52193 ◽  
Author(s):  
Ian R. W. Ritchie ◽  
David J. Dyck
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
High Fat Diet ◽  
Redox State ◽  
Acid Oxidation ◽  
High Fat ◽  
Rapid Loss

scholarly journals Maternal Fat-1 Transgene Protects Offspring from Excess Weight Gain, Oxidative Stress, and Reduced Fatty Acid Oxidation in Response to High-Fat Diet

Nutrients ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 767 ◽  
Author(s):  
Kristen E. Boyle ◽  
Margaret J. Magill-Collins ◽  
Sean A. Newsom ◽  
Rachel C. Janssen ◽  
Jacob E. Friedman
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Fatty Acid ◽  
Weight Gain ◽  
Fatty Acid Oxidation ◽  
High Fat Diet ◽  
Overweight And Obesity ◽  
Acid Oxidation ◽  
High Fat ◽  
Mitochondrial Fatty Acid

Overweight and obesity accompanies up to 70% of pregnancies and is a strong risk factor for offspring metabolic disease. Maternal obesity-associated inflammation and lipid profile are hypothesized as important contributors to excess offspring liver and skeletal muscle lipid deposition and oxidative stress. Here, we tested whether dams expressing the fat-1 transgene, which endogenously converts omega-6 (n-6) to omega-3 (n-3) polyunsaturated fatty acid, could protect wild-type (WT) offspring against high-fat diet induced weight gain, oxidative stress, and disrupted mitochondrial fatty acid oxidation. Despite similar body mass at weaning, offspring from fat-1 high-fat-fed dams gained less weight compared with offspring from WT high-fat-fed dams. In particular, WT males from fat-1 high-fat-fed dams were protected from post-weaning high-fat diet induced weight gain, reduced fatty acid oxidation, or excess oxidative stress compared with offspring of WT high-fat-fed dams. Adult offspring of WT high-fat-fed dams exhibited greater skeletal muscle triglycerides and reduced skeletal muscle antioxidant defense and redox balance compared with offspring of WT dams on control diet. Fat-1 offspring were protected from the reduced fatty acid oxidation and excess oxidative stress observed in offspring of WT high-fat-fed dams. These results indicate that a maternal fat-1 transgene has protective effects against offspring liver and skeletal muscle lipotoxicity resulting from a maternal high-fat diet, particularly in males. Altering maternal fatty acid composition, without changing maternal dietary composition or weight gain with high-fat feeding, may highlight important strategies for n-3-based prevention of developmental programming of obesity and its complications.

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 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.

RS4-type resistant starch prevents high-fat diet-induced obesity via increased hepatic fatty acid oxidation and decreased postprandial GIP in C57BL/6J mice

2010 ◽  
Vol 298 (3) ◽  
pp. E652-E662 ◽  
Author(s):  
Akira Shimotoyodome ◽  
Junko Suzuki ◽  
Daisuke Fukuoka ◽  
Ichiro Tokimitsu ◽  
Tadashi Hase
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Resistant Starch ◽  
High Fat Diet ◽  
Acid Oxidation ◽  
High Fat ◽  
Fat Utilization ◽  
Hepatic Fatty Acid ◽  
Diet Induced Obesity ◽  
Hepatic Fatty Acid Oxidation

Chemically modified starches (CMS) are RS4-type resistant starch, which shows a reduced availability, as well as high-amylose corn starch (HACS, RS2 type), compared with the corresponding unmodified starch. Previous studies have shown that RS4 increases fecal excretion of bile acids and reduces zinc and iron absorption in rats. The aim of this study was to investigate the effects of dietary RS4 supplementation on the development of diet-induced obesity in mice. Weight- and age-matched male C57BL/6J mice were fed for 24 wk on a high-fat diet containing unmodified starch, hydroxypropylated distarch phosphate (RS4), or HACS (RS2). Those fed the RS4 diet had significantly lower body weight and visceral fat weight than those fed either unmodified starch or the RS2 diet. Those fed the RS4 diet for 4 wk had a significantly higher hepatic fatty acid oxidation capacity and related gene expression and lower blood insulin than those fed either unmodified starch or the RS2 diet. Indirect calorimetry showed that the RS4 group exhibited higher energy expenditure and fat utilization compared with the RS2 group. When gavaged with fat (trioleate), RS4 stimulated a lower postprandial glucose-dependent insulinotropic polypeptide (GIP; incretin) response than RS2. Higher blood GIP levels induced by chronic GIP administration reduced fat utilization in high-fat diet-fed mice. In conclusion, dietary supplementation with RS4-type resistant starch attenuates high-fat diet-induced obesity more effectively than RS2 in C57BL/6J mice, which may be attributable to lower postprandial GIP and increased fat catabolism in the liver.

scholarly journals MON-672 Progesterone Receptor Membrane Component 1 Suppresses Lipid Accumulation and Lipotoxicity in Animal Model of Diabetic Cardiomyopathy (DCM)

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Sang R Lee ◽  
Eui-ju Hong
Keyword(s):  
Fatty Acid ◽  
Progesterone Receptor ◽  
Fatty Acid Oxidation ◽  
Diabetic Cardiomyopathy ◽  
Mitochondrial Respiration ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
Acid Oxidation ◽  
High Fat ◽  
Membrane Component

Abstract Diabetic cardiomyopathy (DCM) is one of the complications triggered by type II diabetes (T2D) (1). When free fatty acids (FFA) are abundant in insulin resistant pre-diabetic patients because of adipose lipolysis, FFA tends to move toward heart (2). Lipid accumulation can cause cardiac lipotoxicity and exacerbate DCM (3). In previous study, Pgrmc1 has been identified to associate with fatty acid synthesis (4). Therefore, we assumed that Pgrmc1 will associate with DCM. By feeding high-fat diet for 8 weeks and injecting streptozotocin (30mg/kg), T2D and DCM were induced. The lipid accumulation was exacerbated in T2D-induced Pgrmc1 KO heart, and FFA level was also high. Levels of lipid metabolic genes showed the tendency for lipid accumulation and lipotoxicity, and glycolysis was induced in T2D-induced Pgrmc1 KO heart. Though glycolysis presents higher efficiency for energy production in cardiomyopathy (5), it did not compensate the impairment of mitochondrial respiration in Pgrmc1 KO heart. High-fat diet and streptozotocin could not be the interfering factors, because suppression of fatty acid oxidation, induction of glycolysis, and impairment of mitochondrial respiration were observed similarly in post-prandial mice which were fed with normal chow. Insulin was excluded for interfering factor as cell line with serum starvation showed mitochondrial suppression and glycolytic induction in flux analyzer analysis in Pgrmc1 knockdown. Conversely, induction of fatty acid oxidation and suppression of glycolysis were observed in 72 h fasting of Pgrmc1 KO heart, suggesting the nutrition is closely associated with the metabolic modulation of Pgrmc1 on heart. This metabolic phenotype of Pgrmc1 KO heart consequently exacerbated DCM by showing high levels of fibrosis, inflammation, endoplasmic reticulum stress, and oxidative stress. References: (1) Jia G, Hill MA, Sowers JR. Diabetic Cardiomyopathy: An Update of Mechanisms Contributing to This Clinical Entity. Circulation research. 2018;122:624-38. (2) Noll C, Carpentier AC. Dietary fatty acid metabolism in prediabetes. Current opinion in lipidology. 2017;28:1-10. (3) Goldberg IJ, Trent CM, Schulze PC. Lipid metabolism and toxicity in the heart. Cell metabolism. 2012;15:805-12. (4) Lee SR, Kwon SW, Kaya P, Lee YH, Lee JG, Kim G, et al. Loss of progesterone receptor membrane component 1 promotes hepatic steatosis via the induced de novo lipogenesis. Scientific reports. 2018;8:15711. (5) Nagoshi T, Yoshimura M, Rosano GM, Lopaschuk GD, Mochizuki S. Optimization of cardiac metabolism in heart failure. Current pharmaceutical design. 2011;17:3846-53.

scholarly journals Shift in metabolic fuel in acylation-stimulating protein-deficient mice following a high-fat diet

2008 ◽  
Vol 294 (6) ◽  
pp. E1051-E1059 ◽  
Author(s):  
Christian Roy ◽  
Sabina Paglialunga ◽  
Alexandre Fisette ◽  
Patrick Schrauwen ◽  
Esther Moonen-Kornips ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
Energy Expenditure ◽  
High Fat Diet ◽  
Ex Vivo ◽  
Direct Result ◽  
Acid Oxidation ◽  
High Fat ◽  
Metabolic Potential ◽  
Deficient Mice

ASP-deficient mice (C3 KO) have delayed postprandial TG clearance, are hyperphagic, and display increased energy expenditure. Markers of carbohydrate and fatty acid metabolism in the skeletal muscle and heart were examined to evaluate the mechanism. On a high-fat diet, compared with wild-type mice, C3 KO mice have increased energy expenditure, decreased RQ, lower ex vivo glucose oxidation (−39%, P = 0.018), and higher ex vivo fatty acid oxidation (+68%, P = 0.019). They have lower muscle glycogen content (−25%, P < 0.05) and lower activities for the glycolytic enzymes glycogen phosphorylase (−31%, P = 0.005), hexokinase (−43%, P = 0.007), phosphofructokinase (−51%, P < 0.0001), and GAPDH (−15%, P = 0.04). Analysis of mitochondrial enzyme activities revealed that hydroxyacyl-coenzyme A dehydrogenase was higher (+25%, P = 0.004) in C3 KO mice. Furthermore, Western blot analysis of muscle revealed significantly higher fatty acid transporter CD36 (+40%, P = 0.006) and cytochrome c (a marker of mitochondrial content; +69%, P = 0.034) levels in C3 KO mice, whereas the activity of AMP kinase was lower (−48%, P = 0.003). Overall, these results demonstrate a shift in the metabolic potential of skeletal muscle toward increased fatty acid utilization. Whether this is 1) a consequence of decreased adipose tissue storage with repartitioning toward muscle or 2) a direct result of the absence of ASP interaction with the receptor C5L2 in muscle remains to be determined. However, these in vivo data suggest that ASP inhibition could be a potentially viable approach in correcting muscle metabolic dysfunction in obesity.

scholarly journals Western diet, but not high fat diet, causes derangements of fatty acid metabolism and contractile dysfunction in the heart of Wistar rats

2007 ◽  
Vol 406 (3) ◽  
pp. 457-467 ◽  
Author(s):  
Christopher R. Wilson ◽  
Mai K. Tran ◽  
Katrina L. Salazar ◽  
Martin E. Young ◽  
Heinrich Taegtmeyer
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
High Fat Diet ◽  
Ex Vivo ◽  
Western Diet ◽  
Acid Oxidation ◽  
Contractile Dysfunction ◽  
High Fat ◽  
Cardiac Contractile ◽  
Cardiac Contractile Dysfunction

Obesity and diabetes are associated with increased fatty acid availability in excess of muscle fatty acid oxidation capacity. This mismatch is implicated in the pathogenesis of cardiac contractile dysfunction and also in the development of skeletal-muscle insulin resistance. We tested the hypothesis that ‘Western’ and high fat diets differentially cause maladaptation of cardiac- and skeletal-muscle fatty acid oxidation, resulting in cardiac contractile dysfunction. Wistar rats were fed on low fat, ‘Western’ or high fat (10, 45 or 60% calories from fat respectively) diet for acute (1 day to 1 week), short (4–8 weeks), intermediate (16–24 weeks) or long (32–48 weeks) term. Oleate oxidation in heart muscle ex vivo increased with high fat diet at all time points investigated. In contrast, cardiac oleate oxidation increased with Western diet in the acute, short and intermediate term, but not in the long term. Consistent with fatty acid oxidation maladaptation, cardiac power decreased with long-term Western diet only. In contrast, soleus muscle oleate oxidation (ex vivo) increased only in the acute and short term with either Western or high fat feeding. Fatty acid-responsive genes, including PDHK4 (pyruvate dehydrogenase kinase 4) and CTE1 (cytosolic thioesterase 1), increased in heart and soleus muscle to a greater extent with feeding a high fat diet compared with a Western diet. In conclusion, we implicate inadequate induction of a cassette of fatty acid-responsive genes, and impaired activation of fatty acid oxidation, in the development of cardiac dysfunction with Western diet.

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