Reproduction, Fertility and Development Reproduction, Fertility and Development Society
Vertebrate reproductive science and technology
RESEARCH ARTICLE

Fateful triad of reactive oxygen species, mitochondrial dysfunction and lipid accumulation is associated with expression outline of the AMP-activated protein kinase pathway in bovine blastocysts

S. Prastowo A D , A. Amin A E , F. Rings A , E. Held A , D. Salilew Wondim A , A. Gad E , C. Neuhoff A , E. Tholen A , C. Looft A , K. Schellander A , D. Tesfaye A and M. Hoelker A B C F
+ Author Affiliations
- Author Affiliations

A Departement of Animal Breeding and Husbandry Group, University of Bonn, Endenicher Allee 15, 53115 Bonn, Germany.

B Researchstation Frankenforst, Faculty of Agriculture, University of Bonn, Königswinter, Germany.

C Center of Integrated Dairy Research, University of Bonn, Bonn, Germany.

D Animal Science Department, Sebelas Maret University, Surakarta, Indonesia.

E Department of Animal Production, Faculty of Agriculture, Cairo University, Giza, Egypt.

F Corresponding author. Email: mhoe@itw.uni-bonn.de

Reproduction, Fertility and Development 29(5) 890-905 https://doi.org/10.1071/RD15319
Submitted: 13 April 2015  Accepted: 17 December 2015   Published: 24 February 2016

Abstract

Low cryotolerance is considered as the major drawback of in vitro-produced bovine embryos and is frequently associated with a triad encompassing increased cytoplasmic lipid accumulation, enhanced levels of reactive oxygen species (ROS) and mitochondrial dysfunction. The aim of the present study was to explore the role of the AMP-activated protein kinase (AMPK) pathway in the process resulting such phenotypes. Comparative analysis under different environmental conditions revealed downregulation of AMP-activated protein kinase cytalytic subunit 1alpha (AMPKA1), peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1A) and carnitine palmitoyltransferase 1 (CPT1) genes and upregulation of acetyl-CoA carboxylase α (ACC). In contrast, the presence of fatty acids within the culture medium resulted in a distinct molecular profile in the embryo associated with enhanced levels of ROS, mitochondrial dysfunction and elevated lipid accumulation in bovine embryos. Because AMPKA1 regulates PGC1A, CPT1 and ACC, the results of the present study reveal that AMPK in active its form is the key enzyme promoting lipolysis. Because AMPK1 activity is, in turn, controlled by the AMP : ATP ratio, it is possible to speculate that excessive uptake of exogenous free fatty acids could increase cellular ATP levels as a result of the disturbed β-oxidation of these external fatty acids and could therefore bypass that molecular feedback mechanism. Subsequently, this condition would cause enhanced generation of ROS, which negatively affect mitochondrial activity. Both enhanced generation of ROS and low mitochondrial activity are suggested to enhance the accumulation of lipids in bovine embryos.

Additional keyword: mitochondrial activity.


References

Abe, H., and Hoshi, H. (2003). Evaluation of bovine embryos produced in high performance serum-free media. J. Reprod. Dev. 49, 193–202.
Evaluation of bovine embryos produced in high performance serum-free media.CrossRef | 1:CAS:528:DC%2BD3sXmvFSqtLY%3D&md5=78fc5b3262281510baa31bc4f558261fCAS | 14967928PubMed |

Abe, H., Yamashita, S., Satoh, T., and Hoshi, H. (2002). Accumulation of cytoplasmic lipid droplets in bovine embryos and cryotolerance of embryos developed in different culture systems using serum-free or serum-containing media. Mol. Reprod. Dev. 61, 57–66.
Accumulation of cytoplasmic lipid droplets in bovine embryos and cryotolerance of embryos developed in different culture systems using serum-free or serum-containing media.CrossRef | 1:CAS:528:DC%2BD3MXptVejur4%3D&md5=85123b094b0df72cb3538d618eb82f3cCAS | 11774376PubMed |

Agathocleous, M., and Harris, W. A. (2013). Metabolism in physiological cell proliferation and differentiation. Trends Cell Biol. 23, 484–492.
Metabolism in physiological cell proliferation and differentiation.CrossRef | 1:CAS:528:DC%2BC3sXovVeqsb4%3D&md5=5ab7aae15f9c2cc8f6a267947c8688b8CAS | 23756093PubMed |

Alfaradhi, M. Z., Fernandez-Twinn, D. S., Martin-Gronert, M. S., Musial, B., Fowden, A., and Ozanne, S. E. (2014). Oxidative stress and altered lipid homeostasis in the programming of offspring fatty liver by maternal obesity. Am. J. Physiol. Regul. Integr. Comp. Physiol. 307, R26–R34.
Oxidative stress and altered lipid homeostasis in the programming of offspring fatty liver by maternal obesity.CrossRef | 1:CAS:528:DC%2BC2cXhtlSrtLrL&md5=f3ca096c806df71f24027e9f40b284adCAS | 24789994PubMed |

Amin, A., Gad, A., Salilew-Wondim, D., Prastowo, S., Held, E., Hoelker, M., Rings, F., Tholen, E., Neuhoff, C., Looft, C., Schellander, K., and Tesfaye, D. (2014). Bovine embryo survival under oxidative-stress conditions is associated with activity of the NRF2-mediated oxidative-stress-response pathway. Mol. Reprod. Dev. 81, 497–513.
Bovine embryo survival under oxidative-stress conditions is associated with activity of the NRF2-mediated oxidative-stress-response pathway.CrossRef | 1:CAS:528:DC%2BC2cXks1Onsbo%3D&md5=5db8fd3614bc0b053814fbbcee6205b9CAS | 25057524PubMed |

Austin, S., and St-Pierre, J. (2012). PGC1alpha and mitochondrial metabolism emerging concepts and relevance in ageing and neurodegenerative disorders. J. Cell Sci. 125, 4963–4971.
PGC1alpha and mitochondrial metabolism emerging concepts and relevance in ageing and neurodegenerative disorders.CrossRef | 1:CAS:528:DC%2BC3sXitl2htbk%3D&md5=670c9f7391fcaf9d2002759c83cb18b8CAS | 23277535PubMed |

Barceló-Fimbres, M., and Seidel, G. E. (2007a). Effects of either glucose or fructose and metabolic regulators on bovine embryo development and lipid accumulation in vitro. Mol. Reprod. Dev. 74, 1406–1418.
Effects of either glucose or fructose and metabolic regulators on bovine embryo development and lipid accumulation in vitro.CrossRef | 17342742PubMed |

Barceló-Fimbres, M., and Seidel, G. E. (2007b). Effects of fetal calf serum, phenazine ethosulfate and either glucose or fructose during in vitro culture of bovine embryos on embryonic development after cryopreservation. Mol. Reprod. Dev. 74, 1395–1405.
Effects of fetal calf serum, phenazine ethosulfate and either glucose or fructose during in vitro culture of bovine embryos on embryonic development after cryopreservation.CrossRef | 17342731PubMed |

Bonnard, C., Durand, A., Peyrol, S., Chanseaume, E., Chauvin, M. A., Morio, B., Vidal, H., and Rieusset, J. (2008). Mitochondrial dysfunction results from oxidative stress in the skeletal muscle of diet-induced insulin-resistant mice. J. Clin. Invest. 118, 789–800.
| 1:CAS:528:DC%2BD1cXhsFOmsL0%3D&md5=8f2a3853110c78e8d16399f74e1895a9CAS | 18188455PubMed |

Boren, J., and Brindle, K. M. (2012). Apoptosis-induced mitochondrial dysfunction causes cytoplasmic lipid droplet formation. Cell Death Differ. 19, 1561–1570.
Apoptosis-induced mitochondrial dysfunction causes cytoplasmic lipid droplet formation.CrossRef | 1:CAS:528:DC%2BC38Xht1WltbzO&md5=53896ecf14cd01299cacb031fa77ed0bCAS | 22460322PubMed |

Burton, G. J., Hempstock, J., and Jauniaux, E. (2003). Oxygen, early embryonic metabolism and free radical-mediated embryopathies. Reprod. Biomed. Online 6, 84–96.
Oxygen, early embryonic metabolism and free radical-mediated embryopathies.CrossRef | 12626148PubMed |

Cagnone, G., and Sirard, M. A. (2014). The impact of exposure to serum lipids during in vitro culture on the transcriptome of bovine blastocysts. Theriogenology 81, 712–722e1–3.
The impact of exposure to serum lipids during in vitro culture on the transcriptome of bovine blastocysts.CrossRef | 1:CAS:528:DC%2BC2cXhtlSlsLw%3D&md5=0ac721c0bbee096dd22b24cbfef1d1ccCAS | 24439163PubMed |

Carling, D. (2004). The AMP-activated protein kinase cascade: a unifying system for energy control. Trends Biochem. Sci. 29, 18–24.
The AMP-activated protein kinase cascade: a unifying system for energy control.CrossRef | 1:CAS:528:DC%2BD2cXjtFeisg%3D%3D&md5=f451c6c3803e6facd261dcc65b3b4747CAS | 14729328PubMed |

Chandrasekaran, K., Hatanpaa, K., Rapoport, S. I., and Brady, D. R. (1997). Decreased expression of nuclear and mitochondrial DNA-encoded genes of oxidative phosphorylation in association neocortex in Alzheimer disease. Brain Res. Mol. Brain Res. 44, 99–104.
Decreased expression of nuclear and mitochondrial DNA-encoded genes of oxidative phosphorylation in association neocortex in Alzheimer disease.CrossRef | 1:CAS:528:DyaK2sXhslemtw%3D%3D&md5=24eb3a1dc90d9d9bd6e2749fc12b96f6CAS | 9030703PubMed |

Clichici, S., Biris, A. R., Tabaran, F., and Filip, A. (2012). Transient oxidative stress and inflammation after intraperitoneal administration of multiwalled carbon nanotubes functionalized with single strand DNA in rats. Toxicol. Appl. Pharmacol. 259, 281–292.
Transient oxidative stress and inflammation after intraperitoneal administration of multiwalled carbon nanotubes functionalized with single strand DNA in rats.CrossRef | 1:CAS:528:DC%2BC38XjtVOqu74%3D&md5=939e15bfd5f81497251cced8a13c1321CAS | 22280989PubMed |

Corton, J. M., Gillespie, J. G., and Hardie, D. G. (1994). Role of the AMP-activated protein kinase in the cellular stress response. Curr. Biol. 4, 315–324.
Role of the AMP-activated protein kinase in the cellular stress response.CrossRef | 1:CAS:528:DyaK2cXktVGqsbg%3D&md5=9bac39fb93edcfa958a3d7a135d1e4f7CAS | 7922340PubMed |

Crosier, A. E., Farin, P. W., Dykstra, M. J., Alexander, J. E., and Farin, C. E. (2001). Ultrastructural morphometry of bovine blastocysts produced in vivo or in vitro. Biol. Reprod. 64, 1375–1385.
Ultrastructural morphometry of bovine blastocysts produced in vivo or in vitro.CrossRef | 1:CAS:528:DC%2BD3MXjtFKqsrw%3D&md5=bc44a5c839d0c7e067ff04a81cdf1c00CAS | 11319141PubMed |

Cui, H., Kong, Y., and Zhang, H. (2012). Oxidative stress, mitochondrial dysfunction, and aging. J. Signal Transduct. 2012, Article ID 646354.
Oxidative stress, mitochondrial dysfunction, and aging.CrossRef |

Dugan, L. L., You, Y. H., Ali, S. S., Diamond-Stanic, M., Miyamoto, S., DeCleves, A. E., Andreyev, A., Quach, T., Ly, S., Shekhtman, G., Nguyen, W., Chepetan, A., Le, T. P., Wang, L., Xu, M., Paik, K. P., Fogo, A., Viollet, B., Murphy, A., Brosius, F., Naviaux, R. K., and Sharma, K. (2013). AMPK dysregulation promotes diabetes-related reduction of superoxide and mitochondrial function. J. Clin. Invest. 123, 4888–4899.
AMPK dysregulation promotes diabetes-related reduction of superoxide and mitochondrial function.CrossRef | 1:CAS:528:DC%2BC3sXhslKksb3O&md5=a6db608a1186e459c3f9719019515ec2CAS | 24135141PubMed |

Dzamko, N., Schertzer, J. D., Ryall, J. G., Steel, R., Macaulay, S. L., Wee, S., Chen, Z. P., Michell, B. J., Oakhill, J. S., Watt, M. J., Jorgensen, S. B., Lynch, G. S., Kemp, B. E., and Steinberg, G. R. (2008). AMPK-independent pathways regulate skeletal muscle fatty acid oxidation. J. Physiol. 586, 5819–5831.
AMPK-independent pathways regulate skeletal muscle fatty acid oxidation.CrossRef | 1:CAS:528:DC%2BD1cXhsFemt7jF&md5=9b9bf99891ddbc4c21fa41fd109838b3CAS | 18845612PubMed |

Ferguson, E. M., and Leese, H. J. (1999). Triglyceride content of bovine oocytes and early embryos. J. Reprod. Fertil. 116, 373–378.
Triglyceride content of bovine oocytes and early embryos.CrossRef | 1:CAS:528:DyaK1MXkslOltbc%3D&md5=a3a50038d8b7e9a43a4aadb2a7a6e68dCAS | 10615263PubMed |

Ferguson, E. M., and Leese, H. J. (2006). A potential role for triglyceride as an energy source during bovine oocyte maturation and early embryo development. Mol. Reprod. Dev. 73, 1195–1201.
A potential role for triglyceride as an energy source during bovine oocyte maturation and early embryo development.CrossRef | 1:CAS:528:DC%2BD28XnvFahtr0%3D&md5=168af4eec6664d066bf7ab1460a49047CAS | 16804881PubMed |

Finkel, T. (2006). Cell biology: a clean energy programme. Nature 444, 151–152.
Cell biology: a clean energy programme.CrossRef | 1:CAS:528:DC%2BD28XhtFyqt7rO&md5=7d9a4b36425a70b34c4aade082802776CAS | 17093435PubMed |

Gad, A., Hoelker, M., Besenfelder, U., Havlicek, V., Cinar, U., Rings, F., Held, E., Dufort, I., Sirard, M. A., Schellander, K., and Tesfaye, D. (2012). Molecular mechanisms and pathways involved in bovine embryonic genome activation and their regulation by alternative in vivo and in vitro culture conditions. Biol. Reprod. 87, 100.
Molecular mechanisms and pathways involved in bovine embryonic genome activation and their regulation by alternative in vivo and in vitro culture conditions.CrossRef | 22811576PubMed |

Gómez, E., Rodríguez, A., Muñoz, M., Caamaño, J. N., Hidalgo, C. O., Morán, E., Facal, N., and Díez, C. (2008). Serum free embryo culture medium improves in vitro survival of bovine blastocysts to vitrification. Theriogenology 69, 1013–1021.
Serum free embryo culture medium improves in vitro survival of bovine blastocysts to vitrification.CrossRef | 18358521PubMed |

Gutiérrez-Adán, A., Lonergan, P., Rizos, D., Ward, F. A., Boland, M. P., Pintado, B., and de la Fuente, J. (2001). Effect of the in vitro culture system on the kinetics of blastocyst development and sex ratio of bovine embryos. Theriogenology 55, 1117–1126.
Effect of the in vitro culture system on the kinetics of blastocyst development and sex ratio of bovine embryos.CrossRef | 11322239PubMed |

Hardie, D. G. (1989). Regulation of fatty acid synthesis via phosphorylation of acetyl-CoA carboxylase. Prog. Lipid Res. 28, 117–146.
Regulation of fatty acid synthesis via phosphorylation of acetyl-CoA carboxylase.CrossRef | 1:STN:280:DyaK3c7hsF2ltg%3D%3D&md5=ae6a15865c5cbf4ad683ff8aa435851dCAS | 2575259PubMed |

Harvey, A. J., Kind, K. L., and Thompson, J. G. (2002). REDOX regulation of early embryo development. Reproduction 123, 479–486.
REDOX regulation of early embryo development.CrossRef | 1:CAS:528:DC%2BD38XivFGhtLk%3D&md5=9d0b58ca96b4f6bc3b50c45da0e655b9CAS | 11914110PubMed |

Henique, C., Mansouri, A., Fumey, G., Lenoir, V., Girard, J., Bouillaud, F., Prip-Buus, C., and Cohen, I. (2010). Increased mitochondrial fatty acid oxidation is sufficient to protect skeletal muscle cells from palmitate-induced apoptosis. J. Biol. Chem. 285, 36 818–36 827.
Increased mitochondrial fatty acid oxidation is sufficient to protect skeletal muscle cells from palmitate-induced apoptosis.CrossRef | 1:CAS:528:DC%2BC3cXhsVWgsrvK&md5=72b697ee163e09ba9f0e05a5e07dbb2eCAS |

Holm, P., Booth, P. J., Schmidt, M. H., Greve, T., and Callesen, H. (1999). High bovine blastocyst development in a static in vitro production system using SOFaa medium supplemented with sodium citrate and myo-inositol with or without serum-proteins. Theriogenology 52, 683–700.
High bovine blastocyst development in a static in vitro production system using SOFaa medium supplemented with sodium citrate and myo-inositol with or without serum-proteins.CrossRef | 1:STN:280:DC%2BD3c7pvVGnsw%3D%3D&md5=5d4c5f6302122967eb232c091decd402CAS | 10734366PubMed |

Hopkins, T. A., Dyck, J. R., and Lopaschuk, G. D. (2003). AMP-activated protein kinase regulation of fatty acid oxidation in the ischaemic heart. Biochem. Soc. Trans. 31, 207–212.
AMP-activated protein kinase regulation of fatty acid oxidation in the ischaemic heart.CrossRef | 1:CAS:528:DC%2BD3sXptF2rsg%3D%3D&md5=2cbb054367a98307c9ca67e098550747CAS | 12546686PubMed |

Hurd, T. R., Prime, T. A., Harbour, M. E., Lilley, K. S., and Murphy, M. P. (2007). Detection of reactive oxygen species-sensitive thiol proteins by redox difference gel electrophoresis: implications for mitochondrial redox signaling. J. Biol. Chem. 282, 22 040–22 051.
Detection of reactive oxygen species-sensitive thiol proteins by redox difference gel electrophoresis: implications for mitochondrial redox signaling.CrossRef | 1:CAS:528:DC%2BD2sXotVGlsLw%3D&md5=3e5b84f7868ba5d6502b527ca31d1e16CAS |

Iossa, S., Mollica, M. P., Lionetti, L., Crescenzo, R., Botta, M., and Liverini, G. (2002). Skeletal muscle oxidative capacity in rats fed high-fat diet. Int. J. Obes. Relat. Metab. Disord. 26, 65–72.
Skeletal muscle oxidative capacity in rats fed high-fat diet.CrossRef | 1:CAS:528:DC%2BD38Xhtleiu7Y%3D&md5=4b4cd2ddf053c67aeda1e4840dbe545eCAS | 11791148PubMed |

Khurana, N. K., and Niemann, H. (2000). Energy metabolism in preimplantation bovine embryos derived in vitro or in vivo. Biol. Reprod. 62, 847–856.
Energy metabolism in preimplantation bovine embryos derived in vitro or in vivo.CrossRef | 1:CAS:528:DC%2BD3cXitFajtrc%3D&md5=4eb6ddb9f1c5e5f3b8b5f47c3b10cc9eCAS | 10727252PubMed |

Korge, P., and Weiss, J. N. (2006). Redox regulation of endogenous substrate oxidation by cardiac mitochondria. Am. J. Physiol. Heart Circ. Physiol. 291, H1436–H1445.
Redox regulation of endogenous substrate oxidation by cardiac mitochondria.CrossRef | 1:CAS:528:DC%2BD28XhtVSksrfI&md5=2dca98c039abed09b3d59596da2ecb9cCAS | 16617125PubMed |

Koves, T. R., Ussher, J. R., Noland, R. C., Slentz, D., Mosedale, M., Ilkayeva, O., Bain, J., Stevens, R., Dyck, J. R., Newgard, C. B., Lopaschuk, G. D., and Muoio, D. M. (2008). Mitochondrial overload and incomplete fatty acid oxidation contribute to skeletal muscle insulin resistance. Cell Metab. 7, 45–56.
Mitochondrial overload and incomplete fatty acid oxidation contribute to skeletal muscle insulin resistance.CrossRef | 1:CAS:528:DC%2BD1cXnsFSnsQ%3D%3D&md5=b34bbfa5a937e8ecddf26f5ea1d55231CAS | 18177724PubMed |

Kumari, U., Ya Jun, W., Huat Bay, B., and Lyakhovich, A. (2014). Evidence of mitochondrial dysfunction and impaired ROS detoxifying machinery in Fanconi anemia cells. Oncogene 33, 165–172.
Evidence of mitochondrial dysfunction and impaired ROS detoxifying machinery in Fanconi anemia cells.CrossRef | 1:CAS:528:DC%2BC3sXnt1ajug%3D%3D&md5=9856a432e7fba4ec9477d3e03c0ced74CAS | 23318445PubMed |

Lee, W. J., Kim, M., Park, H. S., Kim, H. S., Jeon, M. J., Oh, K. S., Koh, E. H., Won, J. C., Kim, M. S., Oh, G. T., Yoon, M., Lee, K. U., and Park, J. Y. (2006). AMPK activation increases fatty acid oxidation in skeletal muscle by activating PPARalpha and PGC-1. Biochem. Biophys. Res. Commun. 340, 291–295.
AMPK activation increases fatty acid oxidation in skeletal muscle by activating PPARalpha and PGC-1.CrossRef | 1:CAS:528:DC%2BD2MXhtlCqtbfP&md5=396a7ea65b6b0335e08c01940dd1b630CAS | 16364253PubMed |

Lee, S. J., Zhang, J., Choi, A. M., and Kim, H. P. (2013). Mitochondrial dysfunction induces formation of lipid droplets as a generalized response to stress. Oxid. Med. Cell. Longev. 2013, Article ID 327167.
Mitochondrial dysfunction induces formation of lipid droplets as a generalized response to stress.CrossRef |

Lenaz, G., Bovina, C., D’Aurelio, M., Fato, R., Formiggini, G., Genova, M. L., Giuliano, G., Merlo Pich, M., Paolucci, U., Parenti Castelli, G., and Ventura, B. (2002). Role of mitochondria in oxidative stress and aging. Ann. N. Y. Acad. Sci. 959, 199–213.
Role of mitochondria in oxidative stress and aging.CrossRef | 1:CAS:528:DC%2BD38XktFWquro%3D&md5=552a576b96ac19f64667cff91418d680CAS | 11976197PubMed |

Li, Y., Xu, S., Mihaylova, M. M., Zheng, B., Hou, X., Jiang, B., Park, O., Luo, Z., Lefai, E., Shyy, J. Y., Gao, B., Wierzbicki, M., Verbeuren, T. J., Shaw, R. J., Cohen, R. A., and Zang, M. (2011). AMPK phosphorylates and inhibits SREBP activity to attenuate hepatic steatosis and atherosclerosis in diet-induced insulin-resistant mice. Cell Metab. 13, 376–388.
AMPK phosphorylates and inhibits SREBP activity to attenuate hepatic steatosis and atherosclerosis in diet-induced insulin-resistant mice.CrossRef | 1:CAS:528:DC%2BC3MXktF2nsLw%3D&md5=aacfc59e112af002470afdddb2daa7b2CAS | 21459323PubMed |

Liu, L., and Keefe, D. L. (2000). Cytoplasm mediates both development and oxidation-induced apoptotic cell death in mouse zygotes. Biol. Reprod. 62, 1828–1834.
Cytoplasm mediates both development and oxidation-induced apoptotic cell death in mouse zygotes.CrossRef | 1:CAS:528:DC%2BD3cXjsF2htrg%3D&md5=7dad50a6636ba2969f5e409a74988e3dCAS | 10819789PubMed |

Lockman, K. A., Baren, J. P., Pemberton, C. J., Baghdadi, H., Burgess, K. E., Plevris-Papaioannou, N., Lee, P., Howie, F., Beckett, G., Pryde, A., Jaap, A. J., Hayes, P. C., Filippi, C., and Plevris, J. N. (2012). Oxidative stress rather than triglyceride accumulation is a determinant of mitochondrial dysfunction in in vitro models of hepatic cellular steatosis. Liver Int. 32, 1079–1092.
Oxidative stress rather than triglyceride accumulation is a determinant of mitochondrial dysfunction in in vitro models of hepatic cellular steatosis.CrossRef | 1:CAS:528:DC%2BC38XhtlOgurzL&md5=47c16d13debe10fb110c188f09f3de71CAS | 22429485PubMed |

Louet, J. F., Hayhurst, G., Gonzalez, F. J., Girard, J., and Decaux, J. F. (2002). The coactivator PGC-1 is involved in the regulation of the liver carnitine palmitoyltransferase I gene expression by cAMP in combination with HNF4 alpha and cAMP-response element-binding protein (CREB). J. Biol. Chem. 277, 37 991–38 000.
The coactivator PGC-1 is involved in the regulation of the liver carnitine palmitoyltransferase I gene expression by cAMP in combination with HNF4 alpha and cAMP-response element-binding protein (CREB).CrossRef | 1:CAS:528:DC%2BD38Xns1Cgtbg%3D&md5=109fd8ea83c46b0d3f2bc566fddaf606CAS |

Marusich, M. F., Robinson, B. H., Taanman, J. W., Kim, S. J., Schillace, R., Smith, J. L., and Capaldi, R. A. (1997). Expression of mtDNA and nDNA encoded respiratory chain proteins in chemically and genetically-derived Rho0 human fibroblasts: a comparison of subunit proteins in normal fibroblasts treated with ethidium bromide and fibroblasts from a patient with mtDNA depletion syndrome. Biochim. Biophys. Acta 1362, 145–159.
Expression of mtDNA and nDNA encoded respiratory chain proteins in chemically and genetically-derived Rho0 human fibroblasts: a comparison of subunit proteins in normal fibroblasts treated with ethidium bromide and fibroblasts from a patient with mtDNA depletion syndrome.CrossRef | 1:CAS:528:DyaK1cXhtlOjtrc%3D&md5=b69269ec1a82ee62126c817db8d7dfabCAS | 9540845PubMed |

Mollica, M. P., Iossa, S., Liverini, G., and Soboll, S. (1999). Stimulation of oxygen consumption following addition of lipid substrates in liver and skeletal muscle from rats fed a high-fat diet. Metabolism 48, 1230–1235.
Stimulation of oxygen consumption following addition of lipid substrates in liver and skeletal muscle from rats fed a high-fat diet.CrossRef | 1:CAS:528:DyaK1MXmslGjtbg%3D&md5=5829417d884fff97ffc27827c034da23CAS | 10535383PubMed |

Morino, K., Petersen, K. F., Sono, S., Choi, C. S., Samuel, V. T., Lin, A., Gallo, A., Zhao, H., Kashiwagi, A., Goldberg, I. J., Wang, H., Eckel, R. H., Maegawa, H., and Shulman, G. I. (2012). Regulation of mitochondrial biogenesis by lipoprotein lipase in muscle of insulin-resistant offspring of parents with type 2 diabetes. Diabetes 61, 877–887.
Regulation of mitochondrial biogenesis by lipoprotein lipase in muscle of insulin-resistant offspring of parents with type 2 diabetes.CrossRef | 1:CAS:528:DC%2BC38XkslCht78%3D&md5=417ed7c294afa4ff903df121f006d2beCAS | 22368174PubMed |

Murphy, M. P. (2013). Mitochondrial dysfunction indirectly elevates ROS production by the endoplasmic reticulum. Cell Metab. 18, 145–146.
Mitochondrial dysfunction indirectly elevates ROS production by the endoplasmic reticulum.CrossRef | 1:CAS:528:DC%2BC3sXht1ems73M&md5=3bf696958d0f47c00fb9ed78902ff0acCAS | 23931748PubMed |

O’Donnell, K. C., Vargas, M. E., and Sagasti, A. (2013). WldS and PGC-1alpha regulate mitochondrial transport and oxidation state after axonal injury. J. Neurosci. 33, 14778–14790.
WldS and PGC-1alpha regulate mitochondrial transport and oxidation state after axonal injury.CrossRef | 1:CAS:528:DC%2BC3sXhsVOltrbM&md5=12395a0a7f9d213d43e3b15865d454a7CAS | 24027278PubMed |

O’Neill, H. M., Holloway, G. P., and Steinberg, G. R. (2013). AMPK regulation of fatty acid metabolism and mitochondrial biogenesis: implications for obesity. Mol. Cell. Endocrinol. 366, 135–151.
AMPK regulation of fatty acid metabolism and mitochondrial biogenesis: implications for obesity.CrossRef | 1:CAS:528:DC%2BC38XhtVOqtLnP&md5=4ab898f471853ad6f44c1f2fff741229CAS | 22750049PubMed |

Oliveira, A. T., Lopes, R. F., and Rodrigues, J. L. (2006). Gene expression and developmental competence of bovine embryos produced in vitro with different serum concentrations. Reprod. Domest. Anim. 41, 129–136.
Gene expression and developmental competence of bovine embryos produced in vitro with different serum concentrations.CrossRef | 1:STN:280:DC%2BD287jtlCgtA%3D%3D&md5=45b94bd9e113be386f2ace4bef9d56cbCAS | 16519718PubMed |

Osler, M. E., and Zierath, J. R. (2008). Adenosine 5′-monophosphate-activated protein kinase regulation of fatty acid oxidation in skeletal muscle. Endocrinology 149, 935–941.
Adenosine 5′-monophosphate-activated protein kinase regulation of fatty acid oxidation in skeletal muscle.CrossRef | 1:CAS:528:DC%2BD1cXisVaqsLk%3D&md5=f13fc6db3d940840e087c4838400f864CAS | 18202133PubMed |

Parrish, J. J., Susko-Parrish, J., Winer, M. A., and First, N. L. (1988). Capacitation of bovine sperm by heparin. Biol. Reprod. 38, 1171–1180.
Capacitation of bovine sperm by heparin.CrossRef | 1:CAS:528:DyaL1cXkslWit7g%3D&md5=5f6eee533fe3840b8dccbb5ba5b04cabCAS | 3408784PubMed |

Rankin, E. B., Rha, J., Selak, M. A., Unger, T. L., Keith, B., Liu, Q., and Haase, V. H. (2009). Hypoxia-inducible factor 2 regulates hepatic lipid metabolism. Mol. Cell. Biol. 29, 4527–4538.
Hypoxia-inducible factor 2 regulates hepatic lipid metabolism.CrossRef | 1:CAS:528:DC%2BD1MXhtVSju7nL&md5=4779f498c9769c7bc75d9e9cd61e5e98CAS | 19528226PubMed |

Rizos, D., Gutierrez-Adan, A., Perez-Garnelo, S., De La Fuente, J., Boland, M. P., and Lonergan, P. (2003). Bovine embryo culture in the presence or absence of serum: implications for blastocyst development, cryotolerance, and messenger RNA expression. Biol. Reprod. 68, 236–243.
Bovine embryo culture in the presence or absence of serum: implications for blastocyst development, cryotolerance, and messenger RNA expression.CrossRef | 1:CAS:528:DC%2BD3sXjtFWj&md5=32337306805acc917a34f73d5b231a5bCAS | 12493719PubMed |

Ruderman, N., and Prentki, M. (2004). AMP kinase and malonyl-CoA: targets for therapy of the metabolic syndrome. Nat. Rev. Drug Discov. 3, 340–351.
AMP kinase and malonyl-CoA: targets for therapy of the metabolic syndrome.CrossRef | 1:CAS:528:DC%2BD2cXis1Gktrc%3D&md5=96162c21db8f5b16ed423646d7edbdffCAS | 15060529PubMed |

Sata, R., Tsujii, H., Abe, H., Yamashita, S., and Hoshi, H. (1999). Fatty acid composition of bovine embryos cultured in serum-free and serum-containing medium during early embryonic development. J. Reprod. Dev. 45, 97–103.
Fatty acid composition of bovine embryos cultured in serum-free and serum-containing medium during early embryonic development.CrossRef | 1:CAS:528:DyaK1MXisFentb4%3D&md5=68c4f667a77a9fb3545e729f2d0d9cfdCAS |

Shoubridge, E. A. (2001). Nuclear genetic defects of oxidative phosphorylation. Hum. Mol. Genet. 10, 2277–2284.
Nuclear genetic defects of oxidative phosphorylation.CrossRef | 1:CAS:528:DC%2BD3MXotVKhsLs%3D&md5=99dc01a74fe4243aaf6de4c55c631b45CAS | 11673411PubMed |

Somfai, T., Kaneda, M., Akagi, S., Watanabe, S., Haraguchi, S., Mizutani, E., Dang-Nguyen, T. Q., Geshi, M., Kikuchi, K., and Nagai, T. (2011). Enhancement of lipid metabolism with l-carnitine during in vitro maturation improves nuclear maturation and cleavage ability of follicular porcine oocytes. Reprod. Fertil. Dev. 23, 912–920.
Enhancement of lipid metabolism with l-carnitine during in vitro maturation improves nuclear maturation and cleavage ability of follicular porcine oocytes.CrossRef | 1:CAS:528:DC%2BC3MXhtVOrtb7M&md5=8b82b0ee3c036f8f4f51570f34110240CAS | 21871210PubMed |

St-Pierre, J., Drori, S., Uldry, M., Silvaggi, J. M., Rhee, J., Jager, S., Handschin, C., Zheng, K., Lin, J., Yang, W., Simon, D. K., Bachoo, R., and Spiegelman, B. M. (2006). Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators. Cell 127, 397–408.
Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators.CrossRef | 1:CAS:528:DC%2BD28XhtFOkt7rM&md5=9e454409394ffce0e87a05d6880947f0CAS | 17055439PubMed |

Stuart, J. A., and Brown, M. F. (2006). Mitochondrial DNA maintenance and bioenergetics. Biochim. Biophys. Acta 1757, 79–89.
Mitochondrial DNA maintenance and bioenergetics.CrossRef | 1:CAS:528:DC%2BD28XisF2nsLc%3D&md5=591bb4e863904d83453c651331c9c12eCAS | 16473322PubMed |

Sturmey, R. G., Reis, A., Leese, H. J., and McEvoy, T. G. (2009). Role of fatty acids in energy provision during oocyte maturation and early embryo development. Reprod. Domest. Anim. 44, 50–58.
Role of fatty acids in energy provision during oocyte maturation and early embryo development.CrossRef | 19660080PubMed |

Sudano, M. J., Paschoal, D. M., Rascado Tda, S., Magalhaes, L. C., Crocomo, L. F., de Lima-Neto, J. F., and Landim-Alvarenga Fda, C. (2011). Lipid content and apoptosis of in vitro-produced bovine embryos as determinants of susceptibility to vitrification. Theriogenology 75, 1211–1220.
Lipid content and apoptosis of in vitro-produced bovine embryos as determinants of susceptibility to vitrification.CrossRef | 1:CAS:528:DC%2BC3MXjs12jtrk%3D&md5=0ccf34a0a0264a5f8c845e847488fd7eCAS | 21247620PubMed |

Tanaka, Y., Aleksunes, L. M., Yeager, R. L., Gyamfi, M. A., Esterly, N., Guo, G. L., and Klaassen, C. D. (2008). NF-E2-related factor 2 inhibits lipid accumulation and oxidative stress in mice fed a high-fat diet. J. Pharmacol. Exp. Ther. 325, 655–664.
NF-E2-related factor 2 inhibits lipid accumulation and oxidative stress in mice fed a high-fat diet.CrossRef | 1:CAS:528:DC%2BD1cXlsVOjt7Y%3D&md5=bde7f62003bc41656051c3faa6cad5eaCAS | 18281592PubMed |

Thomson, D. M., and Winder, W. W. (2009). AMP-activated protein kinase control of fat metabolism in skeletal muscle. Acta Physiol. (Oxf.) 196, 147–154.
AMP-activated protein kinase control of fat metabolism in skeletal muscle.CrossRef | 1:CAS:528:DC%2BD1MXlt1KrtLg%3D&md5=6682bceaaaeb09f913eb0e31d60b6c60CAS | 19245653PubMed |

Tomas, E., Tsao, T. S., Saha, A. K., Murrey, H. E., Zhang Cc, C., Itani, S. I., Lodish, H. F., and Ruderman, N. B. (2002). Enhanced muscle fat oxidation and glucose transport by ACRP30 globular domain: acetyl-CoA carboxylase inhibition and AMP-activated protein kinase activation. Proc. Natl Acad. Sci. USA 99, 16 309–16 313.
Enhanced muscle fat oxidation and glucose transport by ACRP30 globular domain: acetyl-CoA carboxylase inhibition and AMP-activated protein kinase activation.CrossRef | 1:CAS:528:DC%2BD38Xps1ent78%3D&md5=f5df7cd53fa5c8a4c7a16998b758c1ddCAS |

Van Hoeck, V., Rizos, D., Gutierrez-Adan, A., Pintelon, I., Jorssen, E., Dufort, I., Sirard, M. A., Verlaet, A., Hermans, N., Bols, P. E., and Leroy, J. L. (2015). Interaction between differential gene expression profile and phenotype in bovine blastocysts originating from oocytes exposed to elevated non-esterified fatty acid concentrations. Reprod. Fertil. Dev. 27, 372–384.
Interaction between differential gene expression profile and phenotype in bovine blastocysts originating from oocytes exposed to elevated non-esterified fatty acid concentrations.CrossRef | 1:CAS:528:DC%2BC2MXhslegtrc%3D&md5=c2983d160738a33eb399550736a125d2CAS | 24360349PubMed |

Viollet, B., Lantier, L., Devin-Leclerc, J., Hebrard, S., Amouyal, C., Mounier, R., Foretz, M., and Andreelli, F. (2009). Targeting the AMPK pathway for the treatment of Type 2 diabetes. Front. Biosci. () 14, 3380–3400.
Targeting the AMPK pathway for the treatment of Type 2 diabetes.CrossRef | 1:CAS:528:DC%2BD1MXltlWlsrs%3D&md5=3cb9c627bc29b65a66289596c2b05973CAS | 19273282PubMed |

Wilding, M., Coppola, G., Dale, B., and Di Matteo, L. (2009). Mitochondria and human preimplantation embryo development. Reproduction 137, 619–624.
Mitochondria and human preimplantation embryo development.CrossRef | 1:CAS:528:DC%2BD1MXosl2ntLg%3D&md5=8f4aed8f0aa32dd18289ed562ef26909CAS | 19176592PubMed |

Wrenzycki, C., Herrmann, D., Keskintepe, L., Martins, A., Sirisathien, S., Brackett, B., and Niemann, H. (2001). Effects of culture system and protein supplementation on mRNA expression in pre-implantation bovine embryos. Hum. Reprod. 16, 893–901.
Effects of culture system and protein supplementation on mRNA expression in pre-implantation bovine embryos.CrossRef | 1:CAS:528:DC%2BD3MXkt1Cqs74%3D&md5=6916bc091734dbf1daaa86d344e8a7bbCAS | 11331635PubMed |

Wu, S. B., Wu, Y. T., Wu, T. P., and Wei, Y. H. (2014). Role of AMPK-mediated adaptive responses in human cells with mitochondrial dysfunction to oxidative stress. Biochim. Biophys. Acta 1840, 1331–1344.
Role of AMPK-mediated adaptive responses in human cells with mitochondrial dysfunction to oxidative stress.CrossRef | 1:CAS:528:DC%2BC3sXhslOltrfM&md5=bec435ab41789a3e87bcfdb001731fddCAS | 24513455PubMed |

Xu, X. J., Gauthier, M. S., Hess, D. T., Apovian, C. M., Cacicedo, J. M., Gokce, N., Farb, M., Valentine, R. J., and Ruderman, N. B. (2012). Insulin sensitive and resistant obesity in humans: AMPK activity, oxidative stress, and depot-specific changes in gene expression in adipose tissue. J. Lipid Res. 53, 792–801.
Insulin sensitive and resistant obesity in humans: AMPK activity, oxidative stress, and depot-specific changes in gene expression in adipose tissue.CrossRef | 1:CAS:528:DC%2BC38XktlOgtbw%3D&md5=f82b3ab8244a3ded5099d829c4d0f052CAS | 22323564PubMed |

You, M., Matsumoto, M., Pacold, C. M., Cho, W. K., and Crabb, D. W. (2004). The role of AMP-activated protein kinase in the action of ethanol in the liver. Gastroenterology 127, 1798–808.
The role of AMP-activated protein kinase in the action of ethanol in the liver.CrossRef | 1:CAS:528:DC%2BD2MXit1Gisg%3D%3D&md5=5eea96b5379edcb7cfa93ab90c899902CAS | 15578517PubMed |

Zhou, G., Myers, R., Li, Y., Chen, Y., Shen, X., Fenyk-Melody, J., Wu, M., Ventre, J., Doebber, T., Fujii, N., Musi, N., Hirshman, M. F., Goodyear, L. J., and Moller, D. E. (2001). Role of AMP-activated protein kinase in mechanism of metformin action. J. Clin. Invest. 108, 1167–1174.
Role of AMP-activated protein kinase in mechanism of metformin action.CrossRef | 1:CAS:528:DC%2BD3MXns1ChsL4%3D&md5=794b1d7920d475997ecec654253cfe4bCAS | 11602624PubMed |

Zong, H., Ren, J. M., Young, L. H., Pypaert, M., Mu, J., Birnbaum, M. J., and Shulman, G. I. (2002). AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation. Proc. Natl Acad. Sci. USA 99, 15 983–15 987.
AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation.CrossRef | 1:CAS:528:DC%2BD38Xps1egu7s%3D&md5=e8484e0eeb2a797e9887be65e494548dCAS |



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