
DOI . ORG {
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Title[redir]:
Enhanced susceptibility of Cpt1c knockout mice to glucose intolerance induced by a high-fat diet involves elevated hepatic gluconeogenesis and decreased skeletal muscle glucose uptake | Diabetologia
Description:
Aims/hypothesis Carnitine palmitoyltransferase-1 (CPT1)c is a novel isoform in the CPT1 family and is found specifically in the brain. Cpt1c knockout (KO) mice are more susceptible to high-fat diet (HFD)-induced obesity. However, the underlying mechanism of this phenotype and the question of whether CPT1c is involved in the pathogenesis of diet-induced insulin resistance are unclear. Methods To assess the potential role of CPT1c in the regulation of whole-body glucose homeostasis, we generated Cpt1c KO mice and challenged them with HFD or standard chow. Glucose homeostasis of each group was assessed weekly. Results After 8 weeks of HFD feeding, Cpt1c KO mice developed a phenotype of more severe insulin resistance than that in wild-type controls. The increased susceptibility of Cpt1c KO mice to HFD-induced insulin resistance was independent of obesity. Impaired glucose tolerance in Cpt1c KO mice was attributable to elevated hepatic gluconeogenesis and decreased glucose uptake in skeletal muscle. These effects correlated with decreased hepatic and intramuscular fatty acid oxidation and expression of oxidative genes as well as with elevated triacylglycerol content in these tissues. Interestingly, Cpt1c deletion caused a specific elevation of hypothalamic CPT1a and CPT1b isoform expression and activity. We demonstrated that elevated plasma NEFA concentration is one mechanism via which this compensatory effect is induced. Conclusions/interpretation These results further establish the role of CPT1c in controlling whole-body glucose homeostasis and in the regulation of hypothalamic Cpt1 isoform expression. We identify changes in hepatic and skeletal muscle glucose metabolism as important mechanisms determining the phenotype of Cpt1c KO mice.
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Keywords {🔍}
mice, cptc, hfd, glucose, cpt, fig, expression, article, google, scholar, muscle, cas, insulin, pubmed, standard, chow, activity, compared, fatty, bars, skeletal, hypothalamus, acid, increased, hypothalamic, analysis, resistance, feeding, esm, energy, decreased, uptake, weeks, cpta, nefa, cells, homeostasis, carnitine, plasma, metabolism, liver, cptb, mouse, oxidation, pcr, body, group, malonylcoa, study, content,
Topics {✒️}
brain-specific carnitine palmitoyl-transferase-1c malonyl-coa-sensitive carnitine palmitoyltransferase negative pgk-diphtheria toxin long-chain fatty acids fatty acid β-oxidation palmitoylcarnitine-specific transferase activity insulin-stimulated glucose uptake insulin-dependent diabetes mellitus common anti-sense primer increases malonyl-coa concentration related subjects specific palmitoyl-transfer activity 2-deoxy[3h]glucose-6-phosphate diet-induced insulin resistance muscle-specific inflammation induced fat-induced insulin resistance brain-expressed protein related brain-specific cpt1 isoform allosteric inhibitor malonyl-coa fatty acid synthase vector-based rna interference epitope-tagged mouse cpt1c real-time pcr analysis neo–pgk gene cassette real-time pcr analyses fatty acid oxidation hfd-induced insulin resistance cpt1c-dependent alterations occur pgc-1alpha null mice high-fat diet elevated hepatic gluconeogenesis carnitine palmitoyltransferase activity glucose intolerance induced hypothalamic mitochondrial protein decreased glucose uptake lipid metabolism profiles privacy choices/manage cookies hepatic insulin resistance increased hepatic gluconeogenesis acyl-coa molecules analysing hepatic gluconeogenesis hypothalamic malonyl-coa circulating fatty acids peripheral glucose uptake diet-induced obesity muscle glucose uptake hypothalamic cpt1 activity glucose uptake analysis defective energy metabolism adaptive energy metabolism
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headline:Enhanced susceptibility of Cpt1c knockout mice to glucose intolerance induced by a high-fat diet involves elevated hepatic gluconeogenesis and decreased skeletal muscle glucose uptake
description:Carnitine palmitoyltransferase-1 (CPT1)c is a novel isoform in the CPT1 family and is found specifically in the brain. Cpt1c knockout (KO) mice are more susceptible to high-fat diet (HFD)-induced obesity. However, the underlying mechanism of this phenotype and the question of whether CPT1c is involved in the pathogenesis of diet-induced insulin resistance are unclear. To assess the potential role of CPT1c in the regulation of whole-body glucose homeostasis, we generated Cpt1c KO mice and challenged them with HFD or standard chow. Glucose homeostasis of each group was assessed weekly. After 8 weeks of HFD feeding, Cpt1c KO mice developed a phenotype of more severe insulin resistance than that in wild-type controls. The increased susceptibility of Cpt1c KO mice to HFD-induced insulin resistance was independent of obesity. Impaired glucose tolerance in Cpt1c KO mice was attributable to elevated hepatic gluconeogenesis and decreased glucose uptake in skeletal muscle. These effects correlated with decreased hepatic and intramuscular fatty acid oxidation and expression of oxidative genes as well as with elevated triacylglycerol content in these tissues. Interestingly, Cpt1c deletion caused a specific elevation of hypothalamic CPT1a and CPT1b isoform expression and activity. We demonstrated that elevated plasma NEFA concentration is one mechanism via which this compensatory effect is induced. These results further establish the role of CPT1c in controlling whole-body glucose homeostasis and in the regulation of hypothalamic Cpt1 isoform expression. We identify changes in hepatic and skeletal muscle glucose metabolism as important mechanisms determining the phenotype of Cpt1c KO mice.
datePublished:2009-02-18T00:00:00Z
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CPT1 activity
Cpt1 expression
Cpt1c knockout
Fatty acid oxidation
Gluconeogenesis
Glucose intolerance
Glucose uptake
Hypothalamus
Non-esterified fatty acid
Oxidative genes expression
Internal Medicine
Metabolic Diseases
Human Physiology
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headline:Enhanced susceptibility of Cpt1c knockout mice to glucose intolerance induced by a high-fat diet involves elevated hepatic gluconeogenesis and decreased skeletal muscle glucose uptake
description:Carnitine palmitoyltransferase-1 (CPT1)c is a novel isoform in the CPT1 family and is found specifically in the brain. Cpt1c knockout (KO) mice are more susceptible to high-fat diet (HFD)-induced obesity. However, the underlying mechanism of this phenotype and the question of whether CPT1c is involved in the pathogenesis of diet-induced insulin resistance are unclear. To assess the potential role of CPT1c in the regulation of whole-body glucose homeostasis, we generated Cpt1c KO mice and challenged them with HFD or standard chow. Glucose homeostasis of each group was assessed weekly. After 8 weeks of HFD feeding, Cpt1c KO mice developed a phenotype of more severe insulin resistance than that in wild-type controls. The increased susceptibility of Cpt1c KO mice to HFD-induced insulin resistance was independent of obesity. Impaired glucose tolerance in Cpt1c KO mice was attributable to elevated hepatic gluconeogenesis and decreased glucose uptake in skeletal muscle. These effects correlated with decreased hepatic and intramuscular fatty acid oxidation and expression of oxidative genes as well as with elevated triacylglycerol content in these tissues. Interestingly, Cpt1c deletion caused a specific elevation of hypothalamic CPT1a and CPT1b isoform expression and activity. We demonstrated that elevated plasma NEFA concentration is one mechanism via which this compensatory effect is induced. These results further establish the role of CPT1c in controlling whole-body glucose homeostasis and in the regulation of hypothalamic Cpt1 isoform expression. We identify changes in hepatic and skeletal muscle glucose metabolism as important mechanisms determining the phenotype of Cpt1c KO mice.
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dateModified:2009-02-18T00:00:00Z
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CPT1 activity
Cpt1 expression
Cpt1c knockout
Fatty acid oxidation
Gluconeogenesis
Glucose intolerance
Glucose uptake
Hypothalamus
Non-esterified fatty acid
Oxidative genes expression
Internal Medicine
Metabolic Diseases
Human Physiology
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- mx3.zoho.eu
Name Servers:
- josh.ns.cloudflare.com
- zita.ns.cloudflare.com
CDN Services {📦}
- Crossref