High-Fat Diet Increases Fat Oxidation and Promotes Skeletal Muscle Fatty Acid Transporter Expression in Exercise-Trained Mice

2020 ◽  
Vol 23 (3) ◽  
pp. 281-288 ◽  
Author(s):  
Hea-Yeon Yun ◽  
Taein Lee ◽  
Yoonhwa Jeong
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
High Fat Diet ◽  
Fat Oxidation ◽  
High Fat ◽  
Fatty Acid Transporter ◽  
Acid Transporter ◽  
Transporter Expression

scholarly journals Changes in the Diaphragm Lipid Content after Administration of Streptozotocin and High-Fat Diet Regime

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Bartlomiej Lukaszuk ◽  
Agnieszka Miklosz ◽  
Malgorzata Zendzian-Piotrowska ◽  
Beata Wojcik ◽  
Jan Gorski ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acid ◽  
High Fat Diet ◽  
High Fat ◽  
Ceramide Synthesis ◽  
Male Wistar Rats ◽  
Fatty Acid Transporter ◽  
Acid Transporter ◽  
Fatty Acid Species ◽  
Transporter Expression

The diaphragm is a dome-shaped skeletal muscle indispensable for breathing. Its activity contributes up to 70% of the total ventilatory function at rest. In comparison to other skeletal muscles, it is distinguished by an oxidative phenotype and uninterrupted cyclic contraction pattern. Surprisingly, the research regarding diaphragm diabetic phenotype particularly in the light of lipid-induced insulin resistance is virtually nonexistent. Male Wistar rats were randomly allocated into 3 groups: control, streptozotocin-induced (STZ) type-1 diabetes, and rodents fed with high-fat diet (HFD). Additionally, half of the animals from each group were administered with myriocin, a robust, selective inhibitor of ceramide synthesis and, therefore, a potent agent ameliorating insulin resistance. Diaphragm lipid contents were evaluated using chromatography. Fatty acid transporter expression was determined by Western blot. The STZ and HFD rats had increased concentration of lipids, namely, ceramides (CER) and diacylglycerols (DAG). Interestingly, this coincided with an increased concentration of long-chain (C ≥ 16) saturated fatty acid species present in both the aforementioned lipid fractions. The CER/DAG accumulation was accompanied by an elevated fatty acid transporter expression (FATP-1 in HFD and FATP-4 in STZ). Surprisingly, we observed a significantly decreased triacylglycerol content in the diaphragms of STZ-treated rats.

scholarly journals Fatty acid transporter expression and regulation is impaired in placental macrovascular endothelial cells in obese women

2017 ◽  
Vol 32 (6) ◽  
pp. 971-978 ◽  
Author(s):  
Xiaohua Yang ◽  
Patricia Glazebrook ◽  
Geraldine C. Ranasinghe ◽  
Maricela Haghiac ◽  
Virtu Calabuig-Navarro ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Fatty Acid ◽  
Obese Women ◽  
Fatty Acid Transporter ◽  
Acid Transporter ◽  
Transporter Expression

scholarly journals PO-193 Exercise training decreased lipid accumulation in murine skeletal muscle through Sestrin2-mediated SHIP2-JNK signaling pathway

2018 ◽  
Vol 1 (4) ◽  
Author(s):  
Tianyi Wang ◽  
Song Huang ◽  
Xiao Han ◽  
Sujuan Liu ◽  
Yanmei Niu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Exercise Training ◽  
High Fat Diet ◽  
De Novo ◽  
Underlying Mechanism ◽  
Wild Type ◽  
High Fat

Objective Obesity is becoming increasingly prevalent and is an important contributor to the worldwide burden of diseases. It is widely accepted that exercise training is beneficial for the prevention and treatment of obesity. However, the underlying mechanism by which exercise training improving skeletal muscle lipid metabolism is still not fully described. Sestrins (Sestrin1-3) are highly conserved stress-inducible protein. Concomitant ablation of Sestrin2 and Sestrin3 has been reported to provoke hepatic mTORC1/S6K1 activation and insulin resistance even without nutritional overload and obesity, implicating that Sestrin2 and Sestrin3 have an important homeostatic function in the control of mammalian glucose and lipid metabolism. Our previous results demonstrated that physical exercise increased Sestrin2 expression in murine skeletal muscle, while the role of Sestrin2 in regulating lipid metabolism remains unknown.  SH2 domain containing inositol 5-phosphatase (SHIP2) acts as a negative regulator of the insulin signaling both in vitro and in vivo. An increased expression of SHIP2 inhibits the insulin-induced Akt activation, glucose uptake, and glycogen synthesis in 3T3-L1 adipocytes, L6 myotubes and tissues of animal models. Alterations of SHIP2 expression and/or enzymatic function appear to have a profound impact on the development of insulin resistance. However, the regulatory function of SHIP2 in lipid metabolism after exercise remains unclear. It has been reported that SHIP2 modulated lipid metabolism through regulating the activity of c-Jun N-terminal kinase (JNK) and Sterol regulatory element-binding protein-1 (SREBP-1). JNK is a subclass of mitogen-activated protein kinase (MAPK) signaling pathway in mammalian cells and plays a crucial role in metabolic changes and inflammation associated with a high-fat diet. Inhibition of JNK reduces lipid deposition and proteins level of fatty acid de novo synthesis in liver cells. It has been reported that Sestrin2 regulated the phosphorylation of JNK, however the underlying mechanism remains unclear. SREBP-1 is important in regulating cholesterol biosynthesis and uptake and fatty acid biosynthesis, and SREBP-1 expression produces two different isoforms, SREBP-1a and SREBP-1c. SREBP-1c is responsible for regulating the genes required for de novo lipogenesis and its expression is regulated by insulin. SREBP-1a regulates genes related to lipid and cholesterol production and its activity is regulated by sterol levels in the cell. Altogether, the purpose of this study was to explore the effect and underlying mechanism of Sestrin2 on lipid accumulation after exercise training. Methods Male wild type and SESN2−/− mice were divided into normal chow (NC) and high-fat diet (HFD) groups to create insulin resistance mice model. After 8 weeks the IR model group was then divided into HFD sedentary control and HFD exercise groups (HE). Mice in HE group underwent 6-week treadmill exercise to reveal the effect of exercise training on lipid metabolism in insulin resistance model induced by HFD. We explored the mechanism through which Sestrin2 regulated lipid metabolism in vitro by supplying palmitate, overexpressing or inhibiting SESNs, SHIP2 and JNK in myotubes. Results We found that 6-week exercise training decreased body weight, BMI and fat mass in wild type and SESN2-/- mice after high-fat diet (HFD) feeding. And exercise training decreased the level of plasma glucose, serum insulin, triglycerides and free fatty acids in wild type but not in Sestrin2-/- mice. Lipid droplet in skeletal muscle was also decreased in wild type but did not in Sestrin2-/- mice. Moreover, exercise training increased the proteins expression involved in fatty acid oxidation and decreased the proteins which related to fatty acid de novo synthesis. The results of oil red staining and the change of proteins related to fatty acid de novo synthesis and beta oxidation in myotubes treated with palmitate, Ad-SESN2 and siRNA-Sestrin2 were consisted with the results in vivo, which suggested that Sestrin2 was a key regulator in lipid metabolism. Exercise training increased Sestrin2 expression and reversed up-regulation of SHIP2 and pJNK induced by HFD in wild type mice but not in Sestrin2-/- mice. In parallel, overexpression of Sestrin2 decreased the level of SHIP2 and pJNK induced by palmitate while Sestrin2 knock down by siRNA-Sestrin2 treatment did not change the expression of SHIP2 and pJNK, which suggested that Sestrin2 modulated SHIP2 and JNK in the state of abnormal lipid metabolism. Inhibition of SHIP2 reduced the activity of JNK, increased lipid accumulation and the proteins of fatty acid synthesis after palmitate treatment and over expression of Sestrin2, which suggest that Sestrin2 modulated lipid metabolism through SHIP2/JNK pathway. Conclusions Sestrin2 plays an important role in improving lipid metabolism after exercise training, and Sestrin2 regulates lipid metabolism by SHIP2-JNK pathway in skeletal muscle.

scholarly journals Effects of three different conjugated linoleic acid preparations on insulin signalling, fat oxidation and mitochondrial function in rats fed a high-fat diet

2007 ◽  
Vol 98 (2) ◽  
pp. 264-275 ◽  
Author(s):  
Joo Sun Choi ◽  
In-Uk Koh ◽  
Myeong Ho Jung ◽  
Jihyun Song
Keyword(s):  
Insulin Resistance ◽  
Fatty Acid ◽  
Linoleic Acid ◽  
Mitochondrial Function ◽  
High Fat Diet ◽  
Insulin Signalling ◽  
Fat Oxidation ◽  
Acid Oxidation ◽  
High Fat ◽  
Cla Isomers

To investigate the effects of three different conjugated linoleic acid (CLA) preparations containing different ratios of CLA isomers on insulin signalling, fatty acid oxidation and mitochondrial function, Sprague–Dawley rats were fed a high-fat diet either unsupplemented or supplemented with one of three CLA preparations at 1 % of the diet for 8 weeks. The first CLA preparation contained approximately 30 % cis-9, trans-11 (c9, t11)-CLA isomer and 40 % trans-10, cis-12 (t10, c12)-CLA isomer (CLA-mix). The other two preparations were an 80:20 mix (c9, t11-CLA-mix) or a 10:90 mix of two CLA isomers (t10, c12-CLA-mix). Insulin resistance was decreased in all three supplemented groups based on the results of homeostasis model assessment and the revised quantitative insulin-sensitivity check index. The phosphorylation of insulin receptor substrate-1 on serine decreased in the livers of all three supplemented groups, while subsequent Akt phosphorylation increased only in the t10, c12-CLA-mix group. Both the c9, t11-CLA-mix and the t10, c12-CLA-mix increased the expression of hepatic adiponectin receptors R1 and 2, which are thought to enhance insulin sensitivity and fat oxidation. The c9, t11-CLA-mix increased protein and mRNA levels of PPARα, acyl-CoA oxidase and uncoupling protein, which are involved in fatty acid oxidation and energy dissipation. The c9, t11-CLA-mix enhanced mitochondrial function and protection against oxidative stress by increasing the activities of cytochrome c oxidase, manganese-superoxide dismutase, glutathione peroxidase, and glutathione reductase and the level of GSH. In conclusion, all three CLA preparations reduced insulin resistance. Among them, the c9, t11-CLA-mix was the most effective based on the parameters reflecting insulin resistance and fat oxidation, and mitochondrial antioxidative enzyme activity in the liver.

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 CTRP9 transgenic mice are protected from diet-induced obesity and metabolic dysfunction

2013 ◽  
Vol 305 (5) ◽  
pp. R522-R533 ◽  
Author(s):  
Jonathan M. Peterson ◽  
Zhikui Wei ◽  
Marcus M. Seldin ◽  
Mardi S. Byerly ◽  
Susan Aja ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Transgenic Mice ◽  
High Fat Diet ◽  
Fat Oxidation ◽  
Acid Oxidation ◽  
Ampk Activation ◽  
High Fat ◽  
Diet Induced Obesity

CTRP9 is a secreted multimeric protein of the C1q family and the closest paralog of the insulin-sensitizing adipokine, adiponectin. The metabolic function of this adipose tissue-derived plasma protein remains largely unknown. Here, we show that the circulating levels of CTRP9 are downregulated in diet-induced obese mice and upregulated upon refeeding. Overexpressing CTRP9 resulted in lean mice that dramatically resisted weight gain induced by a high-fat diet, largely through decreased food intake and increased basal metabolism. Enhanced fat oxidation in CTRP9 transgenic mice resulted from increases in skeletal muscle mitochondrial content, expression of enzymes involved in fatty acid oxidation (LCAD and MCAD), and chronic AMPK activation. Hepatic and skeletal muscle triglyceride levels were substantially decreased in transgenic mice. Consequently, CTRP9 transgenic mice had a greatly improved metabolic profile with markedly reduced fasting insulin and glucose levels. The high-fat diet-induced obesity, insulin resistance, and hepatic steatosis observed in wild-type mice were prevented in transgenic mice. Consistent with the in vivo data, recombinant protein significantly enhanced fat oxidation in L6 myotubes via AMPK activation and reduced lipid accumulation in H4IIE hepatocytes. Collectively, these data establish CTRP9 as a novel metabolic regulator and a new component of the metabolic network that links adipose tissue to lipid metabolism in skeletal muscle and liver.

scholarly journals The RabGAPs TBC1D1 and TBC1D4 control uptake of long-chain fatty acids into skeletal muscle via fatty acid transporter SLC27A4/FATP4 Short title: RabGAPs in skeletal muscle lipid metabolism

2020 ◽  
Author(s):  
Ada Admin ◽  
Tim Benninghoff ◽  
Lena Espelage ◽  
Samaneh Eickelschulte ◽  
Isabel Zeinert ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Long Chain Fatty Acids ◽  
Muscle Lipid ◽  
Skeletal Muscle Lipid ◽  
Fatty Acid Transporter ◽  
Acid Transporter ◽  
Long Chain

The two closely related RabGTPase-activating proteins (RabGAPs) TBC1D1 and TBC1D4 play a crucial role in the regulation of GLUT4 translocation in response to insulin and contraction in skeletal muscle. In mice, deficiency in one or both RabGAPs leads to reduced insulin and contraction-stimulated glucose uptake, and to elevated fatty acid uptake and oxidation in both glycolytic and oxidative muscle fibers without altering mitochondrial copy number and the abundance of OXPHOS proteins. Here we present evidence for a novel mechanism of skeletal muscle lipid utilization involving the two RabGAPs and the fatty acid transporter SLC27A4/FATP4. Both RabGAPs control the uptake of saturated and unsaturated long-chain fatty acids (LCFAs) into skeletal muscle and knockdown of a subset of RabGAP substrates, <i>Rab8, Rab10 </i>or <i>Rab14, </i>decreased LCFA uptake into these cells. In skeletal muscle from <i>Tbc1d1/Tbc1d4</i> knockout animals, SLC27A4/FATP4 abundance was increased and depletion of SLC27A4/FATP4 but not FAT/CD36 completely abrogated the enhanced fatty acid oxidation in RabGAP-deficient skeletal muscle and cultivated C2C12 myotubes. Collectively, our data demonstrate that RabGAP-mediated control of skeletal muscle lipid metabolism converges with glucose metabolism at the level of downstream RabGTPases and involves regulated transport of LCFAs via SLC27A4/FATP4.

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