Regulation of fatty acid synthesis and degradation by the AMP-activated protein kinase

2002 ◽  
Vol 30 (5) ◽  
pp. A102-A102
Author(s):  
D.G. Hardie
Keyword(s):  
Fatty Acid ◽  
Protein Kinase ◽  
Fatty Acid Synthesis ◽  
Acid Synthesis ◽  
Amp Activated Protein Kinase ◽  
Synthesis And Degradation

Regulation of fatty acid synthesis and oxidation by the AMP-activated protein kinase

2002 ◽  
Vol 30 (6) ◽  
pp. 1064-1070 ◽  
Author(s):  
D. G. Hardie ◽  
D. A. Pan
Keyword(s):  
Fatty Acid ◽  
Protein Kinase ◽  
Fatty Acid Oxidation ◽  
Fatty Acid Synthesis ◽  
Cellular Stress ◽  
Energy Charge ◽  
Acid Synthesis ◽  
Atp Depletion ◽  
Acid Oxidation ◽  
Amp Activated Protein Kinase

The AMP-activated protein kinase (AMPK) is a sensor of cellular energy charge and a ‘metabolic master switch’. When activated by ATP depletion, it switches off ATP-consuming processes, while switching on catabolic pathways that generate ATP. AMPK exists as heterotrimeric complexes comprising catalytic α subunits and regulatory β and γ subunits, each of which occurs as multiple isoforms. Rising AMP and falling ATP, brought about by various types of cellular stress (including exercise in skeletal muscle), stimulate the system in an ultrasensitive manner. Acetyl-CoA carboxylase (ACC) exists in mammals as two isoforms, termed ACC-1 and ACC-2 (also known as ACC-α and ACC-β). AMPK phosphorylates and inactivates both isoforms at the equivalent site. Knockout mice, and other approaches, suggest that the malonyl-CoA produced by ACC-2 is exclusively involved in regulation of fatty acid oxidation, whereas that produced by ACC-1 is utilized in fatty acid synthesis. Activation of AMPK by cellular stress or exercise therefore switches on fatty acid oxidation (via phosphorylation of ACC-2) while switching off fatty acid synthesis (via phosphorylation of ACC-1). The Drosophila melanogaster genome contains single genes encoding homologues of the α, β and γ subunits of AMPK (DmAMPK) and of ACC (DmACC). Studies in a Drosophila embryonal cell line show that DmAMPK is activated by stresses that cause ATP depletion (oligomycin, hypoxia or glucose deprivation) and that this is associated with phosphorylation of the site on DmACC equivalent to the AMPK sites on mammalian ACC-1 and ACC-2. This is abolished when expression of DmAMPK is ablated using an RNA interference approach, proving that DmAMPK is necessary for phosphorylation of DmACC in response to ATP depletion.

Regulation of mammalian acetyl-CoA carboxylase

2002 ◽  
Vol 30 (6) ◽  
pp. 1059-1064 ◽  
Author(s):  
M. R. Munday
Keyword(s):  
Fatty Acid ◽  
Protein Kinase ◽  
Critical Role ◽  
Physiological Role ◽  
Acid Synthesis ◽  
Acid Oxidation ◽  
Acetyl Coa Carboxylase ◽  
Acetyl Coa ◽  
Dependent Protein ◽  
Amp Activated Protein Kinase

Acetyl-CoA carboxylase (ACC) plays a critical role in the regulation of fatty acid metabolism and its two isoforms, ACCα and ACCβ, appear to have distinct functions in the control of fatty acid synthesis and fatty acid oxidation, respectively. They are regulated by similar short-term mechanisms of allosteric activation by citrate, and reversible phosphorylation and inactivation, and there is clearly interaction between these mechanisms. AMP-activated protein kinase is the important physiological ACC kinase for both isoforms and yet there is a potential physiological role for cAMP-dependent protein kinase in the hormonally mediated inactivation of ACCα, and phosphorylation of ACCβ in its unique N-terminus.

scholarly journals Regulation of gene expression by glucose

1999 ◽  
Vol 58 (3) ◽  
pp. 621-623 ◽  
Author(s):  
P. Ferré
Keyword(s):  
Fatty Acid ◽  
Protein Kinase ◽  
Transcriptional Activation ◽  
Fatty Acid Synthase ◽  
Regulatory Element ◽  
Regulation Of Gene Expression ◽  
Acid Synthesis ◽  
Glucose Response ◽  
Amp Activated Protein Kinase ◽  
Fatty Acid Synthase Gene

Fatty acid synthase (EC 2.3.1.85) is an enzyme involved in the lipogenic pathway allowing fatty acid synthesis from glucose. Glucose up-regulates the transcription of the fatty acid synthase gene in both adipocytes and hepatocytes, with insulin having only an indirect role. The signal metabolite could be glucose-6-phosphate rather than glucose itself. The glucose response element of the fatty acid synthase gene has not yet been precisely identified, although a −2 kb region of the fatty acid synthase promoter is sufficient to confer nutritional responsiveness to a reporter gene. ADD1/SREBP1, a b-HLH-LZ transcription factor belonging to the sterol regulatory element-binding protein family might be involved in the transduction of the glucose effect. Finally, the stimulatory effect of glucose on the expression of the fatty acid synthase gene is inhibited by the activation of AMP-activated protein kinase. Interestingly enough, AMP-activated protein kinase is structurally and functionally related to the yeast SNF1 protein kinase complex which is essential for the transcriptional activation of glucose-repressed genes in Saccharomyces cerevisiae.

scholarly journals Glucagon regulates ACC activity in adipocytes through the CAMKKβ/AMPK pathway

2012 ◽  
Vol 302 (12) ◽  
pp. E1560-E1568 ◽  
Author(s):  
I-Chen Peng ◽  
Zhen Chen ◽  
Wei Sun ◽  
Ying-Shiuan Li ◽  
Traci LaNai Marin ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Protein Kinase ◽  
Fatty Acid Synthesis ◽  
Acid Synthesis ◽  
Dependent Protein Kinase ◽  
Ampk Signaling ◽  
Dependent Protein

Glucagon is important for regulating lipid metabolism in part through its inhibition of fatty acid synthesis in adipocytes. Acetyl-CoA carboxylase 1 (ACC1) is the rate-limiting enzyme for fatty acid synthesis. Glucagon has been proposed to activate cAMP-dependent protein kinase A (PKA), which phosphorylates ACC1 to attenuate the lipogenic activity of ACC1. Because AMP-activated protein kinase (AMPK) also inhibits fatty acid synthesis by phosphorylation of ACC1, we examined the involvement of AMPK and its upstream kinase in the glucagon-elicited signaling in adipocytes in vitro and in vivo. LC-MS-MS analysis suggested that ACC1 was phosphorylated only at Ser79, an AMPK-specific site, in glucagon-treated adipocytes. Pharmacological inhibitors and siRNA knockdown of AMPK or PKA in adipocytes demonstrate that glucagon regulates ACC1 and ACC2 activity through AMPK but not PKA. By using Ca2+/calmodulin-dependent protein kinase kinase-β knockout (CaMKKβ−/−) mice and cultured adipocytes, we further show that glucagon activates the CaMKKβ/AMPK/ACC cascade. Additionally, fasting increases the phosphorylation of AMPK and ACC in CaMKKβ+/+ but not CaMKKβ−/− mice. These results indicate that CaMKKβ/AMPK signaling is an important molecular component in regulating lipid metabolism in adipocytes responding to glucagon and could be a therapeutic target for the dysregulation of energy storage.

Dissimilar regulation of glucose and lipid metabolism by leptin in two strains of gibel carp (Carassius gibelio)

2020 ◽  
pp. 1-15
Author(s):  
Liyun Wu ◽  
Hongyan Li ◽  
Wenjie Xu ◽  
Bo Dong ◽  
Junyan Jin ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Protein Kinase ◽  
Fatty Acid Synthesis ◽  
Acid Synthesis ◽  
Signalling Pathway ◽  
Janus Kinase ◽  
Gibel Carp ◽  
Glucose And Lipid Metabolism ◽  
Nutritional Studies

Abstract Previous nutritional studies have shown that insulin regulation is different between DT and A strains of gibel carp. As leptin plays a pivotal role in the effects of insulin, we hypothesised that leptin regulation of glucose and lipid metabolism would differ between the two strains. To test our hypothesis, recombinant human leptin was injected into two strains. The results showed that leptin activated the phosphatidylinositol 3-kinase (PI3K)–protein kinase B (AKT), AMP-activated protein kinase–acetyl coenzyme A carboxylase and Janus kinase 2 (JAK2)–signal transducer and activator of transcription (STAT) signalling pathways in both strains. Hypoglycaemia induced by leptin might be due to higher glucose uptake by the liver and muscles together with enhanced glycolytic potential and reduced gluconeogenic potential. Decreased lipogenesis and up-regulated fatty acid oxidation were induced by leptin. In terms of genotype, the PI3K–AKT signalling pathway was more strongly activated by leptin in the muscle tissue of the A strain, as reflected by the heightened phosphorylation of AKT. Furthermore, glycogen content, glycolytic enzyme activity and gluconeogenic capability were higher in the A strain than the DT strain. Strain A had higher levels of fatty acid synthesis and lipolytic capacity in the liver than the DT strain, but the opposite was true in white muscle. Regarding leptin–genotype interactions, the DT strain displayed stronger regulation of glucose metabolism in the liver by leptin as compared with the A strain. Moreover, a more active JAK2–STAT signalling pathway accompanied by enhanced inhibition of fatty acid synthesis by leptin was observed in the DT strain. Overall, the regulation of glucose and lipid metabolism by leptin differed between the two strains, as expected.

scholarly journals Fatty Acid Synthesis and Degradation Interplay to Regulate the Oxidative Stress in Cancer Cells

2019 ◽  
Vol 20 (6) ◽  
pp. 1348 ◽  
Author(s):  
Valeryia Mikalayeva ◽  
Ieva Ceslevičienė ◽  
Ieva Sarapinienė ◽  
Vaidotas Žvikas ◽  
Vytenis Skeberdis ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Cancer Cells ◽  
Fatty Acid Synthesis ◽  
Breast Cancer Cells ◽  
Lipid Synthesis ◽  
Acid Synthesis ◽  
Acid Oxidation ◽  
Mitochondrial Fatty Acid Oxidation ◽  
Mitochondrial Fatty Acid ◽  
Synthesis And Degradation

Both cytosolic fatty acid synthesis (FAS) and mitochondrial fatty acid oxidation (FAO) have been shown to play a role in the survival and proliferation of cancer cells. This study aimed to confirm experimentally whether FAS and FAO coexist in breast cancer cells (BCC). By feeding cells with 13C-labeled glutamine and measuring labeling patterns of TCA intermediates, it was possible to show that part of the cytosolic acetyl-CoA used in lipid synthesis is also fed back into the mitochondrion via fatty acid degradation. This results in the transfer of reductive potential from the cytosol (in the form of NADPH) to the mitochondrion (in the form of NADH and FADH2). The hypothesized mechanism was further confirmed by blocking FAS and FAO with siRNAs. Exposure to staurosporine (which induces ROS production) resulted in the disruption of simultaneous FAS and FAO, which could be explained by NADPH depletion.

In silico Mapping and Structure Analysis of Key Enzyme Genes in Fatty Acid Synthesis of Soybean

2009 ◽  
Vol 35 (10) ◽  
pp. 1942-1947
Author(s):  
Wan-Kun SONG ◽  
Ming-Xi ZHU ◽  
Yang-Lin ZHAO ◽  
Jing WANG ◽  
Wen-Fu LI ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Structure Analysis ◽  
Fatty Acid Synthesis ◽  
In Silico ◽  
Acid Synthesis ◽  
In Silico Mapping ◽  
Key Enzyme
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