Hypertriglyceridemia increases mitochondrial resting respiration and susceptibility to permeability transition.
High plasma level of triglycerides (TGs) is a common feature in atherosclerosis, obesity, diabetes, alcoholism, stress, and infection. Since mitochondria have been implicated in cell death under a variety of metabolic disorders, we examined liver mitochondrial functions in hypertriglyceridemic transgenic mice. Hypertriglyceridemia increased resting respiration and predisposed to mitochondrial permeability transition (MPT). Ciprofibrate therapy reduced plasma TG levels, normalized respiration, and prevented MPT. The higher resting respiration in transgenic mitochondria remained in the presence of the adenine nucleotide carrier inhibitor, carboxyatractyloside, bovine serum albumin, and the uncoupling proteins (UCPs) inhibitor, GDP. UCP2 content was similar in both control and transgenic mitochondria. We propose that faster resting respiration represents a regulated adaptation to oxidize excess free fatty acid in the transgenic mice.
Alberici
Luciane C
LC
Depto. Patologia Clínica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, 13083-970 Campinas, São Paulo, Brazil.
Oliveira
Helena C F
HC
Bighetti
Eliete J B
EJ
de Faria
Eliana C
EC
Degaspari
Giovana R
GR
Souza
Claudio T
CT
Vercesi
Anibal E
AE
D000818:Animals; D001278:Atractyloside / Q000031:analogs & derivatives* / Q000494:pharmacology; D019069:Cell Respiration / Q000187:drug effects / Q000502:physiology; D002995:Clofibric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D058607:Fibric Acids; D006153:Guanosine Diphosphate / Q000494:pharmacology; D015228:Hypertriglyceridemia / Q000188:drug therapy / Q000378:metabolism*; D000960:Hypolipidemic Agents / Q000494:pharmacology; D007473:Ion Channels; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D026901:Membrane Transport Proteins / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D014280:Triglycerides / Q000097:blood / Q000378:metabolism*; D000071246:Uncoupling Protein 2
D058607:Fibric Acids; D000960:Hypolipidemic Agents; D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D014280:Triglycerides; C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2; D006153:Guanosine Diphosphate; D001278:Atractyloside; D012710:Serum Albumin, Bovine; D002995:Clofibric Acid; C019304:ciprofibrate; C003853:carboxyatractyloside