title: Cold tolerance, cold-induced hyperphagia, and nonshivering thermogenesis are normal in α₁-AMPK-/- mice.
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(1)-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(3)-adrenergic agonist). Under control conditions, loss of α(1)-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(2)-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(1)-AMPK(-/-) and wild-type mice. Similarly, the degree of cold-induced hyperphagia was identical in the two groups. We conclude that α(1)-AMPK does not play an obligatory role in these processes and that adaptations to chronic loss of α(1)-AMPK are able to compensate for its loss via several mechanisms.
authors: Department of Medicine, University of Wisconsin, Madison, Wisconsin, USA.
authors: Jake D
authors: JD
authors: Bauwens
authors: Eric G
authors: EG
authors: Schmuck
authors: Christopher R
authors: CR
authors: Lindholm
authors: Rebecca L
authors: RL
authors: Ertel
authors: Jacob D
authors: JD
authors: Mulligan
authors: Ian
authors: I
authors: Hovis
authors: Benoit
authors: B
authors: Viollet
authors: Kurt W
authors: KW
authors: Saupe
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