Impact of endotoxin on UCP homolog mRNA abundance, thermoregulation, and mitochondrial proton leak kinetics

Xing Xian Yu, Jamie L. Barger, Bert B. Boyer, Martin D. Brand, Guohua Pan, Sean H. Adams

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Abstract

Linking tissue uncoupling protein (UCP) homolog abundance with functional metabolic outcomes and with expression of putative genetic regulators promises to better clarify UCP homolog physiological function. A murine endotoxemia model characterized by marked alterations in thermoregulation was employed to examine the association between heat production, UCP homolog expression, and mitochondrial proton leak ('uncoupling'). After intraperitoneal lipopolysaccharide (LPS, ≃6 mg/kg) injection, colonic temperature (T(c)) in adult female C57BL6/J mice dropped to a nadir of ≃30°C by 8 h, preceded by a four- to fivefold drop in liver UCP2 and UCP5/brain mitochondrial carrier protein 1 mRNA levels, with no change in their hindlimb skeletal muscle (SKM) expression. SKM UCP3 mRNA rose fivefold during development of hypothermia and was correlated with an LPS-induced increase in plasma free fatty acid concentration. UCP2 and UCP5 transcripts recovered about three- to sixfold in both tissues starting at 6-8 h, preceding a recovery of T(c) between 16 and 24 h. SKM UCP3 followed an opposite pattern. Such results are not consistent with an important influence of UCP3 in driving heat production but do not preclude a role for UCP2 or UCP5 in this process. The transcription coactivator PGC-1 displayed a transient LPS-evoked rise (threefold) or drop (two- to fivefold) in SKM and liver expression, respectively. No differences between control and LPS-treated mouse liver or SKM in vitro mitochondrial proton leak were evident at time points corresponding to large differences in UCP homolog expression.

Original languageEnglish (US)
Pages (from-to)E433-E446
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume279
Issue number2 42-2
StatePublished - Sep 14 2000

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Keywords

  • Hypothermia
  • Lipopolysaccharide
  • Metabolic rate
  • Peroxisome proliferator-activated receptor
  • Uncoupling proteins

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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