title: Metabolic gene switching in the murine female heart parallels enhanced mitochondrial respiratory function in response to oxidative stress.
abstract: The mechanisms underlying increased cardioprotection in younger female mice are unclear. We hypothesized that serine-threonine protein kinase (protein kinase B; Akt) triggers a metabolic gene switch (decreased fatty acids, increased glucose) in female hearts to enhance mitochondrial bioenergetic capacity, conferring protection against oxidative stress. Here, we employed male and female control (db/+) and obese (db/db) mice. We found diminished transcript levels of peroxisome proliferator-activated receptor-alpha, muscle-type carnitine palmitoyltransferase 1 and pyruvate dehydrogenase kinase 4 in female control hearts versus male hearts. Moreover, females displayed improved recovery of cardiac mitochondrial respiratory function and higher ATP levels versus males in response to acute oxygen deprivation. All these changes were reversed in female db/db hearts. However, we found no significant gender-based differences in levels of Akt, suggesting that Akt-independent signaling mechanisms are responsible for the resilient mitochondrial phenotype observed in female mouse hearts. As glucose is a more energetically efficient fuel substrate when oxygen is limiting, this gene program may be a crucial component that enhances tolerance to oxygen deprivation in female hearts.
authors: Department of Physiological Sciences, Stellenbosch University, South Africa. mfessop@sun.ac.za
authors: M Faadiel
authors: MF
authors: Essop
authors: W Y A
authors: WY
authors: Chan
authors: Heinrich
authors: H
authors: Taegtmeyer
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics*; D004734:Energy Metabolism / Q000235:genetics; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D005947:Glucose / Q000378:metabolism; D006321:Heart / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D008929:Mitochondria, Heart / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010101:Oxygen Consumption; D047493:PPAR alpha / Q000235:genetics*; D011494:Protein Kinases / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012143:Respiratory Physiological Phenomena; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012737:Sex Factors
chemical_list: D005227:Fatty Acids; D047493:PPAR alpha; D000255:Adenosine Triphosphate; D002334:Carnitine O-Palmitoyltransferase; D011494:Protein Kinases; C403287:pyruvate dehydrogenase kinase 4; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose