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http://purl.uniprot.org/citations/29107293http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/29107293http://www.w3.org/2000/01/rdf-schema#comment"

Objective

Excessive hepatic gluconeogenesis is a defining feature of type 2 diabetes (T2D). Most gluconeogenic flux is routed through mitochondria. The mitochondrial pyruvate carrier (MPC) transports pyruvate from the cytosol into the mitochondrial matrix, thereby gating pyruvate-driven gluconeogenesis. Disruption of the hepatocyte MPC attenuates hyperglycemia in mice during high fat diet (HFD)-induced obesity but exerts minimal effects on glycemia in normal chow diet (NCD)-fed conditions. The goal of this investigation was to test whether hepatocyte MPC disruption provides sustained protection from hyperglycemia during long-term HFD and the differential effects of hepatocyte MPC disruption on TCA cycle metabolism in NCD versus HFD conditions.

Method

We utilized long-term high fat feeding, serial measurements of postabsorptive blood glucose and metabolomic profiling and 13C-lactate/13C-pyruvate tracing to investigate the contribution of the MPC to hyperglycemia and altered hepatic TCA cycle metabolism during HFD-induced obesity.

Results

Hepatocyte MPC disruption resulted in long-term attenuation of hyperglycemia induced by HFD. HFD increased hepatic mitochondrial pyruvate utilization and TCA cycle capacity in an MPC-dependent manner. Furthermore, MPC disruption decreased progression of fibrosis and levels of transcript markers of inflammation.

Conclusions

By contributing to chronic hyperglycemia, fibrosis, and TCA cycle expansion, the hepatocyte MPC is a key mediator of the pathophysiology induced in the HFD model of T2D."xsd:string
http://purl.uniprot.org/citations/29107293http://purl.org/dc/terms/identifier"doi:10.1016/j.molmet.2017.09.002"xsd:string
http://purl.uniprot.org/citations/29107293http://purl.uniprot.org/core/author"Fu X."xsd:string
http://purl.uniprot.org/citations/29107293http://purl.uniprot.org/core/author"Burgess S.C."xsd:string
http://purl.uniprot.org/citations/29107293http://purl.uniprot.org/core/author"Taylor E.B."xsd:string
http://purl.uniprot.org/citations/29107293http://purl.uniprot.org/core/author"Cox J.E."xsd:string
http://purl.uniprot.org/citations/29107293http://purl.uniprot.org/core/author"Dupuy A.J."xsd:string
http://purl.uniprot.org/citations/29107293http://purl.uniprot.org/core/author"Gray L.R."xsd:string
http://purl.uniprot.org/citations/29107293http://purl.uniprot.org/core/author"Gibson-Corley K.N."xsd:string
http://purl.uniprot.org/citations/29107293http://purl.uniprot.org/core/author"Feddersen C.R."xsd:string
http://purl.uniprot.org/citations/29107293http://purl.uniprot.org/core/author"Rauckhorst A.J."xsd:string
http://purl.uniprot.org/citations/29107293http://purl.uniprot.org/core/author"Pewa A.D."xsd:string
http://purl.uniprot.org/citations/29107293http://purl.uniprot.org/core/author"Sheldon R.D."xsd:string
http://purl.uniprot.org/citations/29107293http://purl.uniprot.org/core/date"2017"xsd:gYear
http://purl.uniprot.org/citations/29107293http://purl.uniprot.org/core/name"Mol Metab"xsd:string
http://purl.uniprot.org/citations/29107293http://purl.uniprot.org/core/pages"1468-1479"xsd:string
http://purl.uniprot.org/citations/29107293http://purl.uniprot.org/core/title"The mitochondrial pyruvate carrier mediates high fat diet-induced increases in hepatic TCA cycle capacity."xsd:string
http://purl.uniprot.org/citations/29107293http://purl.uniprot.org/core/volume"6"xsd:string
http://purl.uniprot.org/citations/29107293http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/29107293
http://purl.uniprot.org/citations/29107293http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/29107293
http://purl.uniprot.org/uniprot/#_D3Z786-mappedCitation-29107293http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/29107293
http://purl.uniprot.org/uniprot/#_D3Z5S0-mappedCitation-29107293http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/29107293
http://purl.uniprot.org/uniprot/#_D3YWY6-mappedCitation-29107293http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/29107293
http://purl.uniprot.org/uniprot/#_E9Q0V4-mappedCitation-29107293http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/29107293
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