Gene/Protein
Disease
Symptom
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Enzyme
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Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
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Target Concepts:
Gene/Protein
Disease
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Query: EC:2.3.1.21 (
CPT
)
4,580
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Mitochondrial lipid overload in skeletal muscle contributes to insulin resistance, and strategies limiting this lipid pressure improve glucose homeostasis; however, comprehensive cellular adaptations that occur in response to such an intervention have not been reported. Herein, mice with skeletal muscle-specific deletion of
carnitine palmitoyltransferase
1b (Cpt1b
M-/-
), which limits mitochondrial lipid entry, were fed a moderate fat (25%) diet, and samples were subjected to a multimodal analysis merging transcriptomics, proteomics, and nontargeted metabolomics to characterize the coordinated multilevel cellular responses that occur when mitochondrial lipid burden is mitigated. Limiting mitochondrial fat entry predictably improves glucose homeostasis; however, remodeling of glucose metabolism pathways pales compared with adaptations in amino acid and lipid metabolism pathways, shifts in nucleotide metabolites, and biogenesis of mitochondria and peroxisomes. Despite impaired fat utilization, Cpt1b
M-/-
mice have increased acetyl-CoA (14-fold) and
NADH
(2-fold), indicating metabolic shifts yield sufficient precursors to meet energy demand; however, this does not translate to enhance energy status as Cpt1b
M-/-
mice have low ATP and high AMP levels, signifying energy deficit. Comparative analysis of transcriptomic data with disease-associated gene-sets not only predicted reduced risk of glucose metabolism disorders but was also consistent with lower risk for hepatic steatosis, cardiac hypertrophy, and premature death. Collectively, these results suggest induction of metabolic inefficiency under conditions of energy surfeit likely contributes to improvements in metabolic health when mitochondrial lipid burden is mitigated. Moreover, the breadth of disease states to which mechanisms induced by muscle-specific Cpt1b inhibition may mediate health benefits could be more extensive than previously predicted.
...
PMID:Extensive metabolic remodeling after limiting mitochondrial lipid burden is consistent with an improved metabolic health profile. 3109 41
Mitochondrial content is regarded a useful feature to distinguish muscle-fiber types in terms of energy metabolism in skeletal muscles. Increasing evidence suggests that specific mitochondrial bioenergetic phenotypes exist in metabolically different muscle fibers. A few studies have examined the energetic properties of skeletal muscle in domestic fowls; however, no information on muscle bioenergetics in broiler chickens selectively bred for faster growth is available. In this study, we aimed to characterize the mitochondrial contents and functions of chicken skeletal muscle consisting entirely of type I (oxidative) (
M. pubo-ischio-femoralis pars medialis
), type IIA (glycolytic/oxidative) (
M. pubo-ischio-femoralis pars lateralis
), and type IIB (glycolytic) (
M. pectoralis
) muscle fibers. Citrate synthase (CS) activity was the highest in type IIA muscle tissues and isolated mitochondria, among the muscle tissues tested. Although no difference was registered in mitochondrial CS activity between type IIB and type I muscles, tissue CS activity was significantly higher in the latter. Histochemical staining for
NADH
tetrazolium reductase and the ratio of muscle-tissue to mitochondrial CS activity indicated that type I, type IIA, and type IIB muscle-fiber types showed decreasing mitochondrial content. Mitochondria from type I muscle exhibited a higher coupled respiration rate induced by pyruvate/malate, palmitoyl-CoA/malate, and palmitoyl-carnitine, as respiratory substrates, than type IIB-muscle mitochondria, while the response of mitochondria from type IIA muscle to those substrates was comparable to that of mitochondria from type I muscle. Type IIA-muscle mitochondria exhibited the highest
carnitine palmitoyltransferase
-2 level among all tissues tested, which may contribute to the higher fatty acid oxidation in these mitochondria. The results suggest that mitochondrial abundance is one of the features differentiating metabolic characteristics of different chicken skeletal muscle types. Moreover, the study demonstrated that type IIA-muscle mitochondria may have distinct metabolic capacities.
...
PMID:Characterization of Mitochondrial Content and Respiratory Capacities of Broiler Chicken Skeletal Muscles with Different Muscle Fiber Compositions. 3205 77
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