Uncoupling protein 3 and fatty acid metabolism

2001 ◽  
Vol 29 (6) ◽  
pp. 785-791 ◽  
Author(s):  
A. G. Dulloo ◽  
S. Samec ◽  
J. Seydoux
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Lipid Oxidation ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Gene Knockout ◽  
Uncoupling Protein ◽  
Brown Adipose ◽  
Genes Encoding

A role for uncoupling protein (UCP) 3 in fatty acid metabolism is reviewed within the context of our proposal, first put forward in 1998, that this homologue of UCP1 may be involved in the regulation of lipids as fuel substrate rather than in the mediation of thermogenesis. Since then, the demonstrations of muscle-type differences in UCP3 gene regulation in response to dietary manipulations (starvation, high-fat feeding) or to pharmacological interferences with the flux of lipid substrates between adipose-tissue stores and skeletal-muscle mitochondrial oxidation are all in accord with this proposed role for UCP3 in regulating lipids as fuel substrate. However, given the current limitations of gene-knockout technology for evaluating/interpreting the functional importance of genes encoding mitochondrial membrane proteins, the transition from ‘associative’ to ‘cause-and-effect’ evidence for a physiological role of UCP3 in regulating fatty acid metabolism will have to await the development of assays that are sensitive to changes in UCP3 activity. Furthermore, in evaluating the physiological regulators of UCP3, the available evidence points to the existence of adipose-derived factor(s) which, independently of circulating levels of free fatty acids, initiates events leading to the transcription of genes encoding UCP3 and key enzymes of lipid oxidation in the fast glycolytic or fast oxidative-glycolytic muscles, i.e. in the bulk of the skeletal-muscle mass. It is proposed that in tissues where UCP3 co-exists with UCP2 (skeletal muscle, brown adipose tissue, heart) they may act in concert in the overall regulation of lipid oxidation, concomitant to the prevention of lipid-induced oxidative damage.

Role of the AMP-activated protein kinase in regulating fatty acid metabolism during exerciseThis paper is one of a selection of papers published in this Special Issue, entitled 14th International Biochemistry of Exercise Conference – Muscles as Molecular and Metabolic Machines, and has undergone the Journal’s usual peer review process.

2009 ◽  
Vol 34 (3) ◽  
pp. 315-322 ◽  
Author(s):  
Gregory R. Steinberg
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acids ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Protein Kinase ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Moderate Intensity ◽  
Amp Activated Protein Kinase

During moderate-intensity exercise, fatty acids are the predominant substrate for working skeletal muscle. The release of fatty acids from adipose tissue stores, combined with the ability of skeletal muscle to actively fine tune the gradient between fatty acid and carbohydrate metabolism, depending on substrate availability and energetic demands, requires a coordinated system of metabolic control. Over the past decade, since the discovery that AMP-activated protein kinase (AMPK) was increased in accordance with exercise intensity, there has been significant interest in the proposed role of this ancient stress-sensing kinase as a critical integrative switch controlling metabolic responses during exercise. In this review, studies examining the role of AMPK as a regulator of fatty acid metabolism in both adipose tissue and skeletal muscle during exercise will be discussed. Exercise induces activation of AMPK in adipocytes and regulates triglyceride hydrolysis and esterfication through phosphorylation of hormone sensitive lipase (HSL) and glycerol-3-phosphate acyl-transferase, respectively. In skeletal muscle, exercise-induced activation of AMPK is associated with increases in fatty acid uptake, phosphorylation of HSL, and increased fatty acid oxidation, which is thought to occur via the acetyl-CoA carboxylase-malony-CoA-CPT-1 signalling axis. Despite the importance of AMPK in regulating fatty acid metabolism under resting conditions, recent evidence from transgenic models of AMPK deficiency suggest that alternative signalling pathways may also be important for the control of fatty acid metabolism during exercise.

scholarly journals Fatty acid metabolism and the basis of brown adipose tissue function

Adipocyte ◽  
2016 ◽  
Vol 5 (2) ◽  
pp. 98-118 ◽  
Author(s):  
María Calderon-Dominguez ◽  
Joan F. Mir ◽  
Raquel Fucho ◽  
Minéia Weber ◽  
Dolors Serra ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Brown Adipose Tissue ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Brown Adipose

scholarly journals IDH2 Deficiency Is Critical in Myogenesis and Fatty Acid Metabolism in Mice Skeletal Muscle

2020 ◽  
Vol 21 (16) ◽  
pp. 5596
Author(s):  
Jeong Hoon Pan ◽  
Jingsi Tang ◽  
Young Jun Kim ◽  
Jin Hyup Lee ◽  
Eui-Cheol Shin ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Energy Homeostasis ◽  
Muscle Development ◽  
Acid Metabolism ◽  
Uncoupling Protein ◽  
Acid Oxidation ◽  
Oxidative Decarboxylation ◽  
Muscle Weight

Mitochondrial NADP+-dependent isocitrate dehydrogenase (IDH2) catalyzes the oxidative decarboxylation of isocitrate into α-ketoglutarate with concurrent reduction of NADP+ to NADPH. However, it is not fully understood how IDH2 is intertwined with muscle development and fatty acid metabolism. Here, we examined the effects of IDH2 knockout (KO) on skeletal muscle energy homeostasis. Calf skeletal muscle samples from 10-week-old male IDH2 KO and wild-type (WT; C57BL/6N) mice were harvested, and the ratio of skeletal muscle weight to body and the ratio of mitochondrial to nucleic DNA were measured. In addition, genes involved in myogenesis, mitochondria biogenesis, adipogenesis, and thermogenesis were compared. Results showed that the ratio of skeletal muscle weight to body weight was lower in IDH2 KO mice than those in WT mice. Of note, a noticeable shift in fiber size distribution was found in IDH2 KO mice. Additionally, there was a trend of a decrease in mitochondrial content in IDH2 KO mice than in WT mice (p = 0.09). Further, mRNA expressions for myogenesis and mitochondrial biogenesis were either decreased or showed a trend of decrease in IDH2 KO mice. Moreover, genes for adipogenesis pathway (Pparg, Znf423, and Fat1) were downregulated in IDH2 KO mice. Interestingly, mRNA and protein expression of uncoupling protein 1 (UCP1), a hallmark of thermogenesis, were remarkably increased in IDH2 KO mice. In line with the UCP1 expression, IDH2 KO mice showed higher rectal temperature than WT mice under cold stress. Taken together, IDH2 deficiency may affect myogenesis, possibly due to impairments of muscle generation and abnormal fatty acid oxidation as well as thermogenesis in muscle via upregulation of UCP1.

scholarly journals Dietary fatty acid metabolism of brown adipose tissue in cold-acclimated men

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Denis P. Blondin ◽  
Hans C. Tingelstad ◽  
Christophe Noll ◽  
Frédérique Frisch ◽  
Serge Phoenix ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Brown Adipose Tissue ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Dietary Fatty Acid ◽  
Brown Adipose

Fatty acid metabolism in adipose tissue, muscle and liver in health and disease

2006 ◽  
Vol 42 ◽  
pp. 89-103 ◽  
Author(s):  
Keith N. Frayn ◽  
Peter Arner ◽  
Hannele Yki-Järvinen
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Fat Mobilization

Fat is the largest energy reserve in mammals. Most tissues are involved in fatty acid metabolism, but three are quantitatively more important than others: adipose tissue, skeletal muscle and liver. Each of these tissues has a store of triacylglycerol that can be hydrolysed (mobilized) in a regulated way to release fatty acids. In the case of adipose tissue, these fatty acids may be released into the circulation for delivery to other tissues, whereas in muscle they are a substrate for oxidation and in liver they are a substrate for re-esterification within the endoplasmic reticulum to make triacylglycerol that will be secreted as very-low-density lipoprotein. These pathways are regulated, most clearly in the case of adipose tissue. Adipose tissue fat storage is stimulated, and fat mobilization suppressed, by insulin, leading to a drive to store energy in the fed state. Muscle fatty acid metabolism is more sensitive to physical activity, during which fatty acid utilization from extracellular and intracellular sources may increase enormously. The uptake of fat by the liver seems to depend mainly upon delivery in the plasma, but the secretion of very-low-density lipoprotein triacylglycerol is suppressed by insulin. There is clearly cooperation amongst the tissues, so that, for instance, adipose tissue fat mobilization increases to meet the demands of skeletal muscle during exercise. When triacylglycerol accumulates excessively in skeletal muscle and liver, sometimes called ectopic fat deposition, then the condition of insulin resistance arises. This may reflect a lack of exercise and an excess of fat intake.

scholarly journals Arterio-venous balance studies of skeletal muscle fatty acid metabolism: what can we believe?

2013 ◽  
Vol 305 (8) ◽  
pp. E925-E930 ◽  
Author(s):  
ZengKui Guo ◽  
Michael D. Jensen
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acids ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Healthy Humans ◽  
Venous Circulation ◽  
Complex Anatomy ◽  
Muscle Groups

The arterio-venous balance (A-V balance/difference) technique has been used by a number of groups, including ours, to study skeletal muscle fatty acid metabolism. Several lines of evidence indicate that, like glycogen, intramyocellular triglycerides (imcTG) are an energy source for local use. As such, the report that increased release of free fatty acids (FFA) via lipolysis from skeletal muscle, but not from adipose tissue, is responsible for the increased systemic lipolysis during IL-6 infusion in healthy humans is somewhat unexpected ( 26 ). It appears that given the complex anatomy of human limbs, as to be discussed in this review, it is virtually impossible to determine whether any fatty acids being released into the venous circulation of an arm or leg derive from the lipolysis of intermuscular fat residing between muscle groups, intramuscular fat residing within muscle groups (between epimysium and perimysium, or bundles), or the intramyocellular triglyceride droplets (imcTG). In many cases, it may even be difficult to be confident that there is no contribution of FFA from subcutaneous adipose tissue. This question is fundamentally important as one attempts to interpret the results of skeletal muscle fatty acid metabolism studies using the A-V balance technique. In this Perspectives article, we examine the reported results of fatty acid kinetics obtained using the techniques to evaluate the degree of and how to minimize contamination when attempting to sample skeletal muscle-specific fatty acids.

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