{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T16:40:11Z","timestamp":1790354411651,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2010,6,8]],"date-time":"2010-06-08T00:00:00Z","timestamp":1275955200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RO1\u2010RR02599"],"award-info":[{"award-number":["RO1\u2010RR02599"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T\u201032\u2010RR00493"],"award-info":[{"award-number":["T\u201032\u2010RR00493"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2010,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mouse models have been designed for a number of fatty acid oxidation defects. Studies in these mouse models have demonstrated that different pathogenetic mechanisms play a role in the pathophysiology of defects of fatty acid oxidation. Supplementation with L\u2010carnitine does not prevent low tissue carnitine levels and induces acylcarnitine production having potentially toxic effects, as presented in very\u2010long\u2010chain acyl\u2010CoA dehydrogenase (VLCAD)\u2010deficient mice. Energy deficiency appears to be an important mechanism in the development of cardiomyopathy and skeletal myopathy in fatty acid oxidation defects and is also the underlying mechanism of cold intolerance. Hypoglycemia as one major clinical sign in all fatty acid oxidation defects occurs due to a reduced hepatic glucose output and an enhanced peripheral glucose uptake rather than to transcriptional changes that are also observed simultaneously, as presented in medium\u2010chain acyl\u2010CoA dehydrogenase (MCAD)\u2010deficient mice. There are reports that an impaired fatty acid oxidation also plays a role in intrauterine life. The embryonic loss demonstrated for some enzyme defects in the mouse supports this hypothesis. However, the exact mechanisms are unknown. This observation correlates to maternal hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome, as observed in pregnancies carrying a long\u2010chain 3\u2010hydroxyacyl\u2010CoA dehydrogenase (LCHAD)\u2010deficient fetus. Synergistic heterozygosity has been shown in isolated patients and in mouse models to be associated with clinical phenotypes common to fatty acid oxidation disorders. Synergistic mutations may also modulate severity of the clinical phenotype and explain in part clinical heterogeneity of fatty acid oxidation defects. In summary, knowledge about the different pathogenetic mechanisms and the resulting pathophysiology allows the development of specific new therapies.<\/jats:p>","DOI":"10.1007\/s10545-010-9121-7","type":"journal-article","created":{"date-parts":[[2010,6,7]],"date-time":"2010-06-07T11:13:54Z","timestamp":1275909234000},"page":"539-546","source":"Crossref","is-referenced-by-count":65,"title":["Mitochondrial fatty acid oxidation disorders: pathophysiological studies in mouse models"],"prefix":"10.1002","volume":"33","author":[{"given":"Ute","family":"Spiekerkoetter","sequence":"first","affiliation":[{"name":"Department of General Pediatrics University Children's Hospital Moorenstr. 5 Duesseldorf 40225 Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip A.","family":"Wood","sequence":"additional","affiliation":[{"name":"Metabolic Signaling &amp; Disease Program, Diabetes and Obesity Research Center Sanford\u2010Burnham Medical Research Institute at Lake Nona Orlando FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2010,6,8]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-199206000-00003"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320470616"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2004.06.001"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.100.22.2248"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1006\/bmme.1996.0033"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.19.2069"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2009.86"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/387090a0"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000088786.19197.E4"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00811.2005"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2006.06.004"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2004.09.010"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI4532"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22284"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1993.1237"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI12590"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2007.10.006"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.26.15592"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2005.07.021"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-006-0199-x"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1203\/PDR.0b013e31816ff6f0"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1053\/plac.2002.0808"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/ilar.43.2.57"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2004.09.006"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2006.02.037"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-007-0548-4"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00246-002-0277-2"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1203\/01.PDR.0000103931.80055.06"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2362.2004.01308.x"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1203\/01.PDR.0000157915.26049.47"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2008.04.002"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-009-1125-9"},{"key":"e_1_2_6_34_1","first-page":"201","article-title":"Impaired cardiac function in very long\u2010chain acyl\u2010CoA dehydrogenase\u2010deficient mice as studied by in\u2010vivo NMR","volume":"30","author":"Veld F","year":"2007","journal-title":"JIMD"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M800221-JLR200"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.0010023"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20041489"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3610417"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1006\/mgme.2000.3066"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1005504223140"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1024433100257"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-198901000-00010"}],"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1007\/s10545-010-9121-7","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1007\/s10545-010-9121-7","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1007\/s10545-010-9121-7","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T15:05:41Z","timestamp":1694790341000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1007\/s10545-010-9121-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,6,8]]},"references-count":41,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2010,10]]}},"alternative-id":["10.1007\/s10545-010-9121-7"],"URL":"https:\/\/doi.org\/10.1007\/s10545-010-9121-7","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,6,8]]}}}