Cold tolerance, cold-induced hyperphagia, and nonshivering thermogenesis are normal in [alpha]^sub 1^-AMPK-/- mice

Recent studies indicate that a substantial amount of metabolically active brown adipose tissue (BAT) exists in adult humans. Given the unique ability of BAT to convert calories to heat, there is intense interest in understanding the regulation of BAT metabolism in hopes that its manipulation might b...

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Published inAmerican journal of physiology. Regulatory, integrative and comparative physiology Vol. 301; no. 2; p. R473
Main Authors Bauwens, Jake D, Schmuck, Eric G, Lindholm, Christopher R, Ertel, Rebecca L, Mulligan, Jacob D, Hovis, Ian, Viollet, Benoit, Saupe, Kurt W
Format Journal Article
LanguageEnglish
Published Bethesda American Physiological Society 01.08.2011
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Abstract Recent studies indicate that a substantial amount of metabolically active brown adipose tissue (BAT) exists in adult humans. Given the unique ability of BAT to convert calories to heat, there is intense interest in understanding the regulation of BAT metabolism in hopes that its manipulation might be an effective way of expending excess calories. Because of the established role of AMP-activated protein kinase (AMPK) as a "metabolic master switch" and its extremely high levels of activity in BAT, it was hypothesized that AMPK might play a central role in regulating BAT metabolism. To test this hypothesis, whole body α...-AMPK... (knockout) and wild-type mice were studied 1) under control (room temperature) conditions, 2) during chronic cold exposure (14 days at 4°C), and 3) during acute nonshivering thermogenesis (injection of a β...-adrenergic agonist). Under control conditions, loss of α...-AMPK resulted in downregulation of two important prothermogenic genes in BAT, thyrotropin-releasing hormone (...9.2-fold) and ciliary neurotrophic factor (-8.7-fold). Additionally, it caused significant upregulation of α...-AMPK activity in BAT, white adipose tissue, and liver, but not cardiac or skeletal muscle. During acute nonshivering thermogenesis and chronic cold exposure, body temperature was indistinguishable in the α...-AMPK... and wild-type mice. Similarly, the degree of cold-induced hyperphagia was identical in the two groups. We conclude that α...-AMPK does not play an obligatory role in these processes and that adaptations to chronic loss of α...-AMPK are able to compensate for its loss via several mechanisms. (ProQuest: ... denotes formulae/symbols omitted.)
AbstractList Recent studies indicate that a substantial amount of metabolically active brown adipose tissue (BAT) exists in adult humans. Given the unique ability of BAT to convert calories to heat, there is intense interest in understanding the regulation of BAT metabolism in hopes that its manipulation might be an effective way of expending excess calories. Because of the established role of AMP-activated protein kinase (AMPK) as a "metabolic master switch" and its extremely high levels of activity in BAT, it was hypothesized that AMPK might play a central role in regulating BAT metabolism. To test this hypothesis, whole body α...-AMPK... (knockout) and wild-type mice were studied 1) under control (room temperature) conditions, 2) during chronic cold exposure (14 days at 4°C), and 3) during acute nonshivering thermogenesis (injection of a β...-adrenergic agonist). Under control conditions, loss of α...-AMPK resulted in downregulation of two important prothermogenic genes in BAT, thyrotropin-releasing hormone (...9.2-fold) and ciliary neurotrophic factor (-8.7-fold). Additionally, it caused significant upregulation of α...-AMPK activity in BAT, white adipose tissue, and liver, but not cardiac or skeletal muscle. During acute nonshivering thermogenesis and chronic cold exposure, body temperature was indistinguishable in the α...-AMPK... and wild-type mice. Similarly, the degree of cold-induced hyperphagia was identical in the two groups. We conclude that α...-AMPK does not play an obligatory role in these processes and that adaptations to chronic loss of α...-AMPK are able to compensate for its loss via several mechanisms. (ProQuest: ... denotes formulae/symbols omitted.)
Author Bauwens, Jake D
Ertel, Rebecca L
Schmuck, Eric G
Mulligan, Jacob D
Lindholm, Christopher R
Viollet, Benoit
Hovis, Ian
Saupe, Kurt W
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Snippet Recent studies indicate that a substantial amount of metabolically active brown adipose tissue (BAT) exists in adult humans. Given the unique ability of BAT to...
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SubjectTerms Genes
Kinases
Metabolism
Rodents
Tissues
Title Cold tolerance, cold-induced hyperphagia, and nonshivering thermogenesis are normal in [alpha]^sub 1^-AMPK-/- mice
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