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

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

Research output: Contribution to journalArticle

61 Citations (Scopus)

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)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume279
Issue number2 42-2
StatePublished - Sep 14 2000
Externally publishedYes

Fingerprint

Body Temperature Regulation
Endotoxins
Protons
Skeletal Muscle
Messenger RNA
Thermogenesis
Liver
Endotoxemia
Mitochondrial Proteins
Hindlimb
Hypothermia
Nonesterified Fatty Acids
Lipopolysaccharides
Carrier Proteins
Mitochondrial Uncoupling Proteins
Injections
Temperature
Brain

Keywords

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

ASJC Scopus subject areas

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

Cite this

Impact of endotoxin on UCP homolog mRNA abundance, thermoregulation, and mitochondrial proton leak kinetics. / Yu, Xing Xian; Barger, Jamie L.; Boyer, Bert; Brand, Martin D.; Pan, Guohua; Adams, Sean H.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 279, No. 2 42-2, 14.09.2000.

Research output: Contribution to journalArticle

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