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The administration of glucose did not rescue the mice under stress conditions, but rewarming alone consistently led to heart rate recovery. Brown adipose tissue (BAT) from the VLCAD<jats:sup>\u2212\/\u2212<\/jats:sup>mice showed elevated levels of the uncoupling protein isoforms and peroxisome proliferator-activated receptor-\u03b1. Biochemical assessment of the VLCAD<jats:sup>\u2212\/\u2212<\/jats:sup>mice BAT showed increased oxygen consumption, attributed to uncoupled respiration in the absence of stress. ADP-stimulated respiration was 23.05 (SD 4.17) and 68.24 (SD 6.3) nmol O<jats:sub>2<\/jats:sub>\u00b7min<jats:sup>\u22121<\/jats:sup>\u00b7mg mitochondrial protein<jats:sup>\u22121<\/jats:sup>for VLCAD<jats:sup>+\/+<\/jats:sup>and VLCAD<jats:sup>\u2212\/\u2212<\/jats:sup>mice, respectively ( P &lt; 0.001), and carbonyl cyanide p-trifluoromethoxyphenylhydrazone-stimulated respiration was 35.9 (SD 3.6) and 49.3 (SD 9) nmol O<jats:sub>2<\/jats:sub>\u00b7min<jats:sup>\u22121<\/jats:sup>\u00b7mg mitochondrial protein<jats:sup>\u22121<\/jats:sup>for VLCAD<jats:sup>+\/+<\/jats:sup>and VLCAD<jats:sup>\u2212\/\u2212<\/jats:sup>mice, respectively ( P &lt; 0.20), but these rates were insufficient to protect them in the cold. We conclude that disturbed mitochondrial bioenergetics in BAT is a critical contributing factor for the cold sensitivity in VLCAD deficiency. Our observations provide insights into the possible mechanisms of stress-induced death in human newborns with abnormal fat metabolism and elucidate targeting of specific substrates for particular metabolic needs.<\/jats:p>","DOI":"10.1152\/ajpheart.00811.2005","type":"journal-article","created":{"date-parts":[[2005,10,1]],"date-time":"2005-10-01T00:25:14Z","timestamp":1128126314000},"page":"H1289-H1297","source":"Crossref","is-referenced-by-count":45,"title":["Abnormal mitochondrial bioenergetics and heart rate dysfunction in mice lacking very-long-chain acyl-CoA dehydrogenase"],"prefix":"10.1152","volume":"290","author":[{"given":"Vernat J.","family":"Exil","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carla D.","family":"Gardner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey N.","family":"Rottman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harold","family":"Sims","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatrijs","family":"Bartelds","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zaza","family":"Khuchua","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rekha","family":"Sindhal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gemin","family":"Ni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arnold W.","family":"Strauss","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1086\/302261"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1993.1368"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1007\/BF00210629"},{"key":"R4","unstructured":"Bennett MJ, Allison F, Pollitt RJ, and Variend S.Fatty acid oxidation defects as causes of unexpected death in infancy.Prog Clin Biol Res321: 349\u2013364, 1990."},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1016\/0925-4439(93)90058-9"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.100.22.2248"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1530\/eje.0.1390001"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2003.022178"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1172\/JCI10947"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1038\/387090a0"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000088786.19197.E4"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1016\/j.ppedcard.2005.04.005"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2004.09.010"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1172\/JCI4532"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(05)82532-6"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1159\/000243301"},{"key":"R17","unstructured":"Hasegawa T, Hori N, and Du W.A case of impairment of mitochondrial fatty acid \u03b2-oxidation.Keio J Med51: 100\u2013106, 2002."},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(71)90123-0"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199403313301308"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(97)01258-1"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.99.10.1337"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1984.64.1.1"},{"key":"R23","unstructured":"Oberkofler H, Dallinger G, Liu YM, Hell E, Krempler F, and Patsch W.Uncoupling protein gene: qualification of expression levels in adipose tissues of obese and non-obese humans.J Lipid Res38: 2125\u20132133, 1997."},{"key":"R24","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81410-5"},{"key":"R25","doi-asserted-by":"crossref","unstructured":"Rashed M, Ozand P, Bennett M, Barnard J, Govindaraju D, and Rinaldo P.Inborn errors of metabolism diagnosed in sudden death cases by acylcarnitine analysis of postmortem bile.Clin Chem41: 1109\u20131114, 1995.","DOI":"10.1093\/clinchem\/41.8.1109"},{"key":"R26","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-199012000-00023"},{"key":"R27","unstructured":"Roe CRand Ding J.Mitochondrial fatty acid oxidation disorders. 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