Mitochondrial overload and incomplete fatty acid oxidation contribute to skeletal muscle insulin resistance.

By T. Koves, J. Ussher, R. Noland, D. Slentz, M. Mosedale, O. Ilkayeva, J. Bain, R. Stevens, J. Dyck, Christopher B. Newgard and 2 more. Cell Metabolism, 2008

1,957 citations recorded by the source corpus.

Subfields: Cell Biology, Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/2f758938a1f7ab9ac3da94abe2ead8808a1909ed

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cell Biology

In Molecular Biology

In Physiology

Citations in the corpus

Cardiac Metabolism in Heart Failure - Implications beyond ATP production (2013, neutral): “These acylcarnitines have been implicated in the pathophysiology of insulin resistance.(15) The reaction catalyzed by CPT I represents a critical regulatory node that determines FA oxidation rates.”
A ceramide-centric view of insulin resistance. (2012, background): “Depletion of malonyl-CoA decarboxylase (MCD), which leads to the accumulation of malonylCoA, increases rates of glucose utilization in vitro (Bouzakri et al., 2008) and in vivo (Koves et al., 2008).”
Mitochondrial fission and remodelling contributes to muscle atrophy (2010, background): “For instance, insulin resistance in humans arises from defects in mitochondrial fatty acid oxidation, which in turn leads to increases in intracellular fatty acid metabolites (fatty acyl CoA and diacylglycerol) that disrupt insulin signalling causing atrophy (Koves et al, 2008).”
Increased Levels of Plasma Acylcarnitines in Obesity and Type 2 Diabetes and Identification of a Marker of Glucolipotoxicity (2010, positive): “Our findings are consistent with recent reports in rodents and in cell culture showing that insulin-resistant skeletal muscle displays increased incomplete β-oxidation, resulting in increased AcylCN intermediates in serum and muscle (9,19,20).”
A Branched-Chain Amino Acid-Related Metabolic Signature that Differentiates Obese and Lean Humans and Contributes to Insulin Resistance (2009, background): “…for mitochondrial 322 Cell Metabolism 9, 311–326, April 8, 2009 ª2009 Elsevier Inc. fuel oxidation in muscle in the same fashion as occurs when HF diet is fed ad-libitum (Koves et al., 2008; Muoio and Newgard, 2008), leading to accumulation of incompletely oxidized lipidderived metabolites.”
Mitochondrial Dysfunction in Diabetes: From Molecular Mechanisms to Functional Significance and Therapeutic Opportunities (2010, positive): “For example, lipid suppression of glucose utilization is mitigated by etomoxir, an inhibitor of carnitine palmitoyl-transferase 1, or by knockdown of malonyl-CoA decarboxylase, an enzyme that promotes mitochondrial b -oxidation by preventing malonyl-CoA–induced inhibition of CPT-I (36, 170).”
Mitochondrial dysfunction: mechanisms and advances in therapy (2024, background): “292 Accumulated intermediates in mitochondria from human muscle with insulin resistance, such as acylcarnitine and ceramide, also suggested the insulin resistance-associated stress pathway either by a de ﬁ ciency in or an overload of mitochondrial oxidative capabilities.”
Cultured gut microbiota from twins discordant for obesity modulate adiposity and metabolic phenotypes in mice (2013, positive): “Obesity-related insulin resistance has been associated with broad-scale accumulation of acylcarnitines in skeletal muscle (46, 47).”
Plasma Ceramides Are Elevated in Obese Subjects With Type 2 Diabetes and Correlate With the Severity of Insulin Resistance (2009, background): “ceramide (35,36) have been implicated in the phenomenon of lipotoxicity.”
Cardiac Metabolism and Its Interactions with Contraction, Growth, and Survival of the Cardiomyocte (2013, background): “In skeletal muscle, increased influx of fatty acid to mitochondria was associated with incomplete oxidation and development of insulin resistance.(108) However, this was not observed in the mouse heart during high-fat feeding(109) or with increased import of long-chain fatty acids to the mitochondri”
A general introduction to the biochemistry of mitochondrial fatty acid β-oxidation (2010, background): “The elevation of free carnitine and, thereby, promotion of the export of acylcarnitines is proposed as a novel therapeutic approach (Koves et al. 2008; Noland et al. 2009; Mynatt 2009; Adams et al. 2009).”
Mitochondrial Dynamics in the Regulation of Nutrient Utilization and Energy Expenditure (2013, background): “…and muscle, mounting evidence suggests that conditions of nutrient excess that increase fuel availability to the mitochondria might modulate bioenergetic efficiency and mitochondrial ATP synthesis capacity (Koves et al., 2008; Bonnard et al., 2008; Rothwell and Stock, 1979; Wikstrom et al., 2007).”
Metabolomics and Metabolic Diseases: Where do we stand? (2016, methodology): “As an early example, targeted metabolomics was used to show increases in a broad array of fatty acid-derived acylcarnitines and a concurrent decrease in TCA cycle intermediates in skeletal muscle of obese rodents (An et al., 2004; Koves et al., 2005, 2008).”
Metabolic flexibility in health and disease (2017, neutral): “Defects in fatty acid oxidation (Kelley et al., 1999; Koves et al., 2008; McGarry, 1992), altered mitochondrial energetics (Lee et al., 2010; Morino et al., 2005), and intramyocellular lipid accumulation (Amati et al., 2011; Coen et al., 2010) have all 1028 Cell Metabolism 25, May 2, 2017 been…”