scholarly journals Exercise Intensity Modulation of Hepatic Lipid Metabolism

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Fábio S. Lira ◽  
Luiz C. Carnevali ◽  
Nelo E. Zanchi ◽  
Ronaldo VT. Santos ◽  
Jean Marc Lavoie ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Exercise Training ◽  
Fatty Acid Oxidation ◽  
Ketone Bodies ◽  
Hepatic Metabolism ◽  
Acid Oxidation ◽  
Hepatic Lipid Metabolism ◽  
Very Low Density Lipoproteins ◽  
Obesity And Cancer

Lipid metabolism in the liver is complex and involves the synthesis and secretion of very low density lipoproteins (VLDL), ketone bodies, and high rates of fatty acid oxidation, synthesis, and esterification. Exercise training induces several changes in lipid metabolism in the liver and affects VLDL secretion and fatty acid oxidation. These alterations are even more conspicuous in disease, as in obesity, and cancer cachexia. Our understanding of the mechanisms leading to metabolic adaptations in the liver as induced by exercise training has advanced considerably in the recent years, but much remains to be addressed. More recently, the adoption of high intensity exercise training has been put forward as a means of modulating hepatic metabolism. The purpose of the present paper is to summarise and discuss the merit of such new knowledge.

scholarly journals Perilipin 5 S155 phosphorylation by PKA is required for the control of hepatic lipid metabolism and glycemic control

2020 ◽  
pp. jlr.RA120001126
Author(s):  
Stacey N Keenan ◽  
William DeNardo ◽  
Jieqiong Lou ◽  
Ralf B. Schittenhelm ◽  
Magdalene K. Montgomery ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Glycemic Control ◽  
Fatty Acid Oxidation ◽  
Lipid Droplet ◽  
Critical Role ◽  
The Body ◽  
Acid Oxidation ◽  
Hepatic Lipid Metabolism ◽  
Hepatic Lipid

Perilipin (PLIN) 5 is a lipid droplet-associated protein that coordinates intracellular lipolysis in highly oxidative tissues and is thought to regulate lipid metabolism in response to phosphorylation by protein kinase A (PKA). We sought to identify PKA phosphorylation sites in PLIN5 and assess their functional relevance in cultured cells and the livers of mice. We detected phosphorylation on S155, S161 and S163 of recombinant PLIN5 by PKA in vitro and identified S155 as a functionally important site for lipid metabolism. Expression of phosphorylation-defective PLIN5 S155A in Plin5 null cells resulted in decreased rates of lipolysis and triglyceride-derived fatty acid oxidation compared with cells expressing wildtype PLIN5. These differences in lipid metabolism were not associated with differences in the cellular distribution of PLIN5. Rather, FLIM-FRET analysis of protein-protein interactions showed that PLIN5 S155 phosphorylation regulates PLIN5 interaction with adipose triglyceride lipase (ATGL) at the lipid droplet, but not with the co-activator of ATGL, α-β hydrolase domain-containing 5 (ABHD5). Re-expression of PLIN5 S155A in the liver of Plin5 liver-specific null mice reduced lipolysis when compared to mice with wildtype PLIN5 re-expression, but was not associated with other changes in hepatic lipid metabolism, such as fatty acid oxidation, de novo lipogenesis and triglyceride secretion. Furthermore, glycemic control was impaired in mice with expression of PLIN5 S155A compared with mice expressing PLIN5. Together, these studies demonstrate that PLIN5 S155 is required for PKA-mediated lipolysis and builds on the body of evidence demonstrating a critical role for PLIN5 in coordinating lipid and glucose metabolism

scholarly journals CDKN2A/p16INK4a suppresses hepatic fatty acid oxidation through the AMPKα2-SIRT1-PPARα signaling pathway

2020 ◽  
Vol 295 (50) ◽  
pp. 17310-17322
Author(s):  
Yann Deleye ◽  
Alexia Karen Cotte ◽  
Sarah Anissa Hannou ◽  
Nathalie Hennuyer ◽  
Lucie Bernard ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Fatty Acid Oxidation ◽  
Lipid Droplet ◽  
Acid Oxidation ◽  
Hepatic Lipid Metabolism ◽  
Hepatic Lipid ◽  
Hepatic Fatty Acid Oxidation

In addition to their well-known role in the control of cellular proliferation and cancer, cell cycle regulators are increasingly identified as important metabolic modulators. Several GWAS have identified SNPs near CDKN2A, the locus encoding for p16INK4a (p16), associated with elevated risk for cardiovascular diseases and type-2 diabetes development, two pathologies associated with impaired hepatic lipid metabolism. Although p16 was recently shown to control hepatic glucose homeostasis, it is unknown whether p16 also controls hepatic lipid metabolism. Using a combination of in vivo and in vitro approaches, we found that p16 modulates fasting-induced hepatic fatty acid oxidation (FAO) and lipid droplet accumulation. In primary hepatocytes, p16-deficiency was associated with elevated expression of genes involved in fatty acid catabolism. These transcriptional changes led to increased FAO and were associated with enhanced activation of PPARα through a mechanism requiring the catalytic AMPKα2 subunit and SIRT1, two known activators of PPARα. By contrast, p16 overexpression was associated with triglyceride accumulation and increased lipid droplet numbers in vitro, and decreased ketogenesis and hepatic mitochondrial activity in vivo. Finally, gene expression analysis of liver samples from obese patients revealed a negative correlation between CDKN2A expression and PPARA and its target genes. Our findings demonstrate that p16 represses hepatic lipid catabolism during fasting and may thus participate in the preservation of metabolic flexibility.

scholarly journals Glucagon-induced extracellular cAMP regulates hepatic lipid metabolism

2017 ◽  
Vol 234 (2) ◽  
pp. 73-87 ◽  
Author(s):  
Sihan Lv ◽  
Xinchen Qiu ◽  
Jian Li ◽  
Jinye Liang ◽  
Weida Li ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Hepatic Steatosis ◽  
Fatty Acid Oxidation ◽  
Lipid Homeostasis ◽  
Acid Oxidation ◽  
Intracellular Camp ◽  
Hepatic Lipid Metabolism ◽  
Hepatic Lipid ◽  
Extracellular Camp

Hormonal signals help to maintain glucose and lipid homeostasis in the liver during the periods of fasting. Glucagon, a pancreas-derived hormone induced by fasting, promotes gluconeogenesis through induction of intracellular cAMP production. Glucagon also stimulates hepatic fatty acid oxidation but the underlying mechanism is poorly characterized. Here we report that following the acute induction of gluconeogenic genes Glucose 6 phosphatase (G6Pase) and Phosphoenolpyruvate carboxykinase (Pepck) expression through cAMP-response element-binding protein (CREB), glucagon triggers a second delayed phase of fatty acid oxidation genes Acyl-coenzyme A oxidase (Aox) and Carnitine palmitoyltransferase 1a (Cpt1a) expression via extracellular cAMP. Increase in extracellular cAMP promotes PPARα activity through direct phosphorylation by AMP-activated protein kinase (AMPK), while inhibition of cAMP efflux greatly attenuates Aox and Cpt1a expression. Importantly, cAMP injection improves lipid homeostasis in fasted mice and obese mice, while inhibition of cAMP efflux deteriorates hepatic steatosis in fasted mice. Collectively, our results demonstrate the vital role of glucagon-stimulated extracellular cAMP in the regulation of hepatic lipid metabolism through AMPK-mediated PPARα activation. Therefore, strategies to improve cAMP efflux could serve as potential new tools to prevent obesity-associated hepatic steatosis.

Atypical antipsychotic drugs perturb AMPK-dependent regulation of hepatic lipid metabolism

2011 ◽  
Vol 300 (4) ◽  
pp. E624-E632 ◽  
Author(s):  
Kyoung-Jin Oh ◽  
Jinyoung Park ◽  
Su Yeon Lee ◽  
Injae Hwang ◽  
Jae Bum Kim ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Fatty Acid Oxidation ◽  
Transcriptional Activity ◽  
Antipsychotic Drugs ◽  
Acid Oxidation ◽  
Phosphorylation Sites ◽  
Hepatic Lipid Metabolism ◽  
Hepatic Lipid ◽  
Ampk Activity

Dysregulation of lipid metabolism is a key feature of metabolic disorder related to side effects of antipsychotic drugs. Here, we investigated the molecular mechanism by which second-generation atypical antipsychotic drugs (AAPDs) affect hepatic lipid metabolism in liver. AAPDs augmented hepatic lipid accumulation by activating expression of sterol regulatory element-binding protein (SREBP) transcription factors, with subsequent induction of downstream target genes involved in lipid and cholesterol synthesis in hepatocytes. We confirmed the direct involvement of SREBPs on AAPD-induced expression of lipogenic and cholesterogenic genes by utilization of adenovirus for dominant negative SREBP (Ad-SREBP-DN). Interestingly, AAPDs significantly decreased phosphorylation of AMPKα and expression of fatty acid oxidation genes. Treatment of constitutive active AMPK restored AAPD-mediated dysregulation of genes involved in both lipid synthesis and fatty acid oxidation. Moreover, AAPDs decreased transcriptional activity of PPARα, a critical transcriptional regulator for controlling hepatic fatty acid oxidation, via an AMPK-dependent manner. Close investigations revealed that mutations at the known p38 MAPK phosphorylation sites (S6/12/21A), but not mutations at the putative AMPKα phosphorylation sites (S167/373/453A), block AAPD-dependent reduction of PPARα transcriptional activity, suggesting that p38 MAPK might be also involved in the regulatory pathway as a downstream effector of AAPDs/AMPK. Taken together, these data suggest that AAPD-stimulated hepatic dysregulation of lipid metabolism could result from the inhibition of AMPK activity, and pharmaceutical means to potentiate AMPK activity would contribute to restore hepatic lipid homeostasis that occurs during AAPD treatment.

Higher mitochondrial fatty acid oxidation following intermittent versus continuous endurance exercise training

1998 ◽  
Vol 76 (9) ◽  
pp. 891-894 ◽  
Author(s):  
P D Chilibeck ◽  
G J Bell ◽  
R P Farrar ◽  
T P Martin
Keyword(s):  
Fatty Acid ◽  
Exercise Training ◽  
Fatty Acid Oxidation ◽  
Endurance Exercise ◽  
High Intensity ◽  
Treadmill Running ◽  
Acid Oxidation ◽  
Interval Exercise ◽  
Endurance Exercise Training ◽  
Mitochondrial Fatty Acid

It has been well documented that skeletal muscle fatty acid oxidation can be elevated by continuous endurance exercise training. However, it remains questionable whether similar adaptations can be induced with intermittent interval exercise training. This study was undertaken to directly compare the rates of fatty acid oxidation in isolated subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria following these different exercise training regimes. Mitochondria were isolated from the gastrocnemius-plantaris muscles of male Sprague-Dawley rats following exercise training 6 days per week for 12 weeks. Exercise training consisted of either continuous, submaximal, endurance treadmill running (n = 10) or intermittent, high intensity, interval running (n = 10). Both modes of training enhanced the oxidation of palmityl-carnitine-malate in both mitochondrial populations (p < 0.05). However, the increase associated with the intermittent, high intensity exercise training was significantly greater than that achieved with the continuous exercise training (p < 0.05). Also, the increases associated with the IMF mitochondria were greater than the SS mitochondria (p < 0.05). These data suggest that high intensity, intermittent interval exercise training is more effective for stimulation of fatty acid oxidation than continuous submaximal exercise training and that this adaptation occurs preferentially within IMF mitochondria.Key words: muscle, subsarcolemmal mitochondria, intermyofibrillar mitochondria.

scholarly journals Editorial: Possible Mechanisms to Explain Abdominal Fat Loss Effect of Exercise Training Other Than Fatty Acid Oxidation

2021 ◽  
Vol 12 ◽  
Author(s):  
Chia-Hua Kuo ◽  
M. Brennan Harris ◽  
Jørgen Arendt Jensen ◽  
Ahmad Alkhatib ◽  
John L. Ivy
Keyword(s):  
Fatty Acid ◽  
Exercise Training ◽  
Fatty Acid Oxidation ◽  
Abdominal Fat ◽  
Acid Oxidation ◽  
Fat Loss ◽  
Loss Effect

Lipid Metabolism and Nutrigenomics – Impact of Sesame Lignans on Gene Expression Profiles and Fatty Acid Oxidation in Rat Liver

2009 ◽  
pp. 10-24 ◽  
Author(s):  
Takashi Ide ◽  
Yasutaka Nakashima ◽  
Hiroshi Iida ◽  
Satoko Yasumoto ◽  
Masumi Katsuta
Keyword(s):  
Gene Expression ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Fatty Acid Oxidation ◽  
Rat Liver ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Acid Oxidation ◽  
Sesame Lignans

scholarly journals Metabolism of rat-liver cell suspensions. 2. Fatty acid oxidation and ketone bodies

1964 ◽  
Vol 92 (3) ◽  
pp. 467-472 ◽  
Author(s):  
JH Exton
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Rat Liver ◽  
Liver Cell ◽  
Ketone Bodies ◽  
Cell Suspensions ◽  
Acid Oxidation

scholarly journals Leptin Augments the Acute Suppressive Effects of Insulin on Hepatic Very Low-Density Lipoprotein Production in Rats

Endocrinology ◽  
2009 ◽  
Vol 150 (5) ◽  
pp. 2169-2174 ◽  
Author(s):  
Wan Huang ◽  
Anantha Metlakunta ◽  
Nikolas Dedousis ◽  
Heidi K. Ortmeyer ◽  
Maja Stefanovic-Racic ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Fatty Acid Oxidation ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Saline Control ◽  
Acid Oxidation ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Vldl Metabolism

It is well established that leptin increases the sensitivity of carbohydrate metabolism to the effects of insulin. Leptin and insulin also have potent effects on lipid metabolism. However, the effects of leptin on the regulation of liver lipid metabolism by insulin have not been investigated. The current study addressed the effects of leptin on insulin-regulated hepatic very low-density lipoprotein (VLDL) metabolism in vivo in rats. A 90-min hyperinsulinemic/euglycemic clamp (4 mU/kg · min−1) reduced plasma VLDL triglyceride (TG) by about 50% (P &lt; 0.001 vs. saline control). Importantly, a leptin infusion (0.2 μg/kg · min−1) in combination with insulin reduced plasma VLDL-TG by about 80% (P &lt; 0.001 vs. insulin alone). These effects did not require altered skeletal muscle lipoprotein lipase activity but did include differential effects of insulin and leptin on liver apolipoprotein (apo) B and TG metabolism. Thus, insulin decreased liver and plasma apoB100/B48 levels (∼50%, P &lt; 0.01), increased liver TGs (∼20%, P &lt; 0.05), and had no effect on fatty acid oxidation. Conversely, leptin decreased liver TGs (∼50%, P &lt; 0.01) and increased fatty acid oxidation (∼50%, P &lt; 0.01) but had no effects on liver or plasma apoB levels. Importantly, the TG-depleting and prooxidative effects of leptin were maintained in the presence of insulin. We conclude that leptin additively increases the suppressive effects of insulin on hepatic and systemic VLDL metabolism by stimulating depletion of liver TGs and increasing oxidative metabolism. The net effect of the combined actions of insulin and leptin is to decrease the production and TG content of VLDL particles.

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