Postburn trauma insulin resistance and fat metabolism

Cree, Melanie G.; Wolfe, Robert R.

doi:10.1152/ajpendo.00562.2007

Cited by 91 publications

(75 citation statements)

References 119 publications

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“…Triglyceride stores develop in sites such as the liver and muscle cells, due to increased FFA delivery following catecholamine-induced lipolysis, decreased ß-oxidation within muscle, and decreased hepatic secretion of fats. These increases in intracellular triglyceride levels may contribute to the observed alterations in insulin signaling (40). In accordance with this, the IMCL accumulation detected by NMR in this study qualifies as a biomarker of altered insulin resistance and signaling in burn trauma.…”

Section: ------------------------------------------------------------supporting

confidence: 86%

Murine intramyocellular lipids quantified by NMR act as metabolic biomarkers in burn trauma

Tzika

Astrakas²,

Cao³

et al. 2008

Int J Mol Med

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Abstract. It has been suggested that intramyocellular lipids (IMCLs) may serve as biomarkers of insulin resistance and mitochondrial dysfunction. Using a hind-limb mouse model of burn trauma, we tested the hypothesis that severe localized burn trauma involving 5% of the total body surface area causes a local increase in IMCLs in the leg skeletal muscle. We quantified IMCLs from ex vivo intact tissue specimens using High-Resolution Magic Angle Spinning (HRMAS) 1 H NMR and characterized the accompanying gene expression patterns in burned versus control skeletal muscle specimens. We also quantified plasma-free fatty acids (FFAs) in burn versus control mice. Our results from HRMAS 1 H NMR measurements indicated that IMCL levels were significantly increased in mice exposed to burn trauma. Furthermore, plasma FFA levels were also significantly increased, and gene expression of Glut4, insulin receptor substrate 1 (IRS1), glycolytic genes, and PGC-1ß was downregulated in these mice. Backward stepwise multiple linear regression analysis demonstrated that IMCL levels correlated significantly with FFA levels, which were a significant predictor of IRS1 and PGC-1ß gene expression. We conclude from these findings that IMCLs can serve as metabolic biomarkers in burn trauma and that FFAs and IMCLs may signal altered metabolic gene expression. This signaling may result in the observed burn-induced insulin resistance and skeletal muscle mitochondrial dysfunction.We believe that IMCLs may therefore be useful biomarkers in predicting the therapeutic effectiveness of hypolipidemic agents for patients with severe burns.

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Section: ------------------------------------------------------------supporting

confidence: 86%

Murine intramyocellular lipids quantified by NMR act as metabolic biomarkers in burn trauma

Tzika

Astrakas²,

Cao³

et al. 2008

Int J Mol Med

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“…Whereas the magnitude of reduction in pyruvate oxidation is in accord with our results, we found no reduction in the oxidation of other mitochondrial substrates, suggesting that more severe trauma is necessary for an overall impairment of mitochondrial oxidative capacity to develop. In support of this notion, burn injury is associated with more profound catabolism and markedly increased lipolysis, plasma FFA, and deposition of triglycerides in skeletal muscle (and liver) (2,12).…”

Section: E617mentioning

confidence: 89%

Skeletal muscle mitochondria exhibit decreased pyruvate oxidation capacity and increased ROS emission during surgery-induced acute insulin resistance

Hagve

Gjessing

Fuskevåg

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

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Hagve M, Gjessing PF, Fuskevåg OM, Larsen TS, Irtun Ø. Skeletal muscle mitochondria exhibit decreased pyruvate oxidation capacity and increased ROS emission during surgery-induced acute insulin resistance. Am J Physiol Endocrinol Metab 308: E613-E620, 2015. First published February 10, 2015; doi:10.1152/ajpendo.00459.2014.-Development of acute insulin resistance represents a negative factor after surgery, but the underlying mechanisms are not fully understood. We investigated the postoperative changes in insulin sensitivity, mitochondrial function, enzyme activities, and release of reactive oxygen species (ROS) in skeletal muscle and liver in pigs on the 2nd postoperative day after major abdominal surgery. Peripheral and hepatic insulin sensitivity were assessed by D-[6,6-2 H2]glucose infusion and hyperinsulinemic euglycemic step clamping. Surgical trauma elicited a decline in peripheral insulin sensitivity (ϳ34%, P Ͻ 0.01), whereas hepatic insulin sensitivity remained unchanged. Intramyofibrillar (IFM) and subsarcolemma mitochondria (SSM) isolated from skeletal muscle showed a postoperative decline in ADP-stimulated respiration (VADP) for pyruvate (ϳ61%, P Ͻ 0.05, and ϳ40%, P Ͻ 0.001, respectively), whereas VADP for glutamate and palmitoyl-Lcarnitine (PC) was unchanged. Mitochondrial leak respiration with PC was increased in SSM (1.9-fold, P Ͻ 0.05) and IFM (2.5-fold, P Ͻ 0.05), indicating FFA-induced uncoupling. The activity of the pyruvate dehydrogenase complex (PDC) was reduced (ϳ32%, P Ͻ 0.01) and positively correlated to the decline in peripheral insulin sensitivity (r ϭ 0.748, P Ͻ 0.05). All other mitochondrial enzyme activities were unchanged. No changes in mitochondrial function in liver were observed. Mitochondrial H2O2 and O2 ·Ϫ emission was measured spectrofluorometrically, and H2O2 was increased in SSM, IFM, and liver mitochondria (ϳ2.3-, ϳ2.5-, and ϳ2.3-fold, respectively, all P Ͻ 0.05). We conclude that an impairment in skeletal muscle mitochondrial PDC activity and pyruvate oxidation capacity arises in the postoperative phase along with increased ROS emission, suggesting a link between mitochondrial function and development of acute postoperative insulin resistance.reactive oxygen species; surgery; insulin resistance; mitochondria; skeletal muscle; liver AFTER SURGERY, the development of an acute transitory state of insulin resistance has been identified as a negative factor associated with increased morbidity and hospital stay (45), but the physiological and molecular mechanisms underlying this condition are not fully elucidated. The decline in insulin sensitivity in the postoperative phase has been thoroughly documented and is reflected mainly by impaired glucose disposal in peripheral tissues, primarily skeletal muscle (21, 36).Oxidative glucose disposal in skeletal muscle is regulated by the pyruvate dehydrogenase complex (PDC), which is an enzyme complex that regulates the flux of glucose-borne pyruvate into the mitochondria by converting pyruvate to acetylCoA, which subsequently enters the ...

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“…Studies that improved insulin sensitivity by low-calorie diets in patients with T2D were accompanied by a reduction in IMTG content (Jazet et al 2008, Lara-Castro et al 2008. Insulin resistance associated with ageing (Nakagawa et al 2007), growth hormone administration (Krag et al 2007) and post-burn trauma (Cree & Wolfe 2008) has been reported to be associated with increased IMTG content. Current opinion is reasonably clear on the fact that IMTG is a useful marker of the level of cytosolic lipid accumulation, but it is more likely that active lipid metabolites such as LCACoAs, DAGs and ceramides or intermediates of FA oxidation pathways interfere with insulin action via a variety of potential mechanisms (Fig.…”

Section: Linking Intramyocellular Triglyceride Content and Insulin Acmentioning

confidence: 99%

Fatty acid metabolism, energy expenditure and insulin resistance in muscle

Turner¹,

Cooney²,

Kraegen³

et al. 2013

Journal of Endocrinology

162

120

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Fatty acids (FAs) are essential elements of all cells and have significant roles as energy substrates, components of cellular structure and signalling molecules. The storage of excess energy intake as fat in adipose tissue is an evolutionary advantage aimed at protecting against starvation, but in much of today's world, humans are faced with an unlimited availability of food, and the excessive accumulation of fat is now a major risk for human health, especially the development of type 2 diabetes (T2D). Since the first recognition of the association between fat accumulation, reduced insulin action and increased risk of T2D, several mechanisms have been proposed to link excess FA availability to reduced insulin action, with some of them being competing or contradictory. This review summarises the evidence for these mechanisms in the context of excess dietary FAs generating insulin resistance in muscle, the major tissue involved in insulin-stimulated disposal of blood glucose. It also outlines potential problems with models and measurements that may hinder as well as help improve our understanding of the links between FAs and insulin action. (C:18:0), oleic acid (C18:1n-9), linoleic acid (C18:2n-6) and, particularly in smaller mammals, arachidonic acid (20:4n-6) and docosahexaenoic acid (22:6n-3). These FAs are the major components of storage triglycerides and cellular membranes, and although C16-C18 FAs are also components of some of the FA-derived signalling molecules (diacylglycerols (DAGs) and ceramides), many of the major lipid signalling molecules (prostaglandins and leukotrienes) are synthesised from very-long-chain, unsaturated FAs (e.g. arachidonic and docosahexaenoic acids) ( Kruger et al. 2010).In the context of the links between excessive lipid storage (obesity) and reduced insulin action (insulin Journal of EndocrinologyThematic Review N TURNER and others Fatty acids and insulin action 220:2 T61-T79

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Postburn trauma insulin resistance and fat metabolism

Abstract: Cree MG, Wolfe RR. Postburn trauma insulin resistance and fat metabolism.

Cited by 91 publications

References 119 publications

Murine intramyocellular lipids quantified by NMR act as metabolic biomarkers in burn trauma

Murine intramyocellular lipids quantified by NMR act as metabolic biomarkers in burn trauma

Skeletal muscle mitochondria exhibit decreased pyruvate oxidation capacity and increased ROS emission during surgery-induced acute insulin resistance

Fatty acid metabolism, energy expenditure and insulin resistance in muscle

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