Uncoupling the agony from ecstasy

Mills, Edward; Banks, Matthew L.; Sprague, Jon E.; Finkel, Toren

doi:10.1038/426403a

Cited by 129 publications

(95 citation statements)

References 10 publications

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“…In the present study, UCP-3 expression was evaluated to provide further validation for the property of the antisense oligonucleotide to inhibit PGC-1␣ expression. However, the results also further support a role for skeletal muscle UCP-3 in thermogenesis, as recently described by Mills and co-workers (23), and evidence that, at least under cold exposure conditions, UCP-3 expression is controlled by the levels of PGC-1␣. When PGC-1␣ expression was inhibited by the antisense oligonucleotide treatment, glucose uptake during the clamp was reduced and GLUT4 migration to the membrane fraction of muscle was significantly impaired.…”

Section: Discussionsupporting

confidence: 58%

Cold-induced PGC-1α expression modulates muscle glucose uptake through an insulin receptor/Akt-independent, AMPK-dependent pathway

Oliveira¹,

Ueno²,

Souza³

et al. 2004

American Journal of Physiology-Endocrinology and Metabolism

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Section: Discussionsupporting

confidence: 58%

Cold-induced PGC-1α expression modulates muscle glucose uptake through an insulin receptor/Akt-independent, AMPK-dependent pathway

Oliveira¹,

Ueno²,

Souza³

et al. 2004

American Journal of Physiology-Endocrinology and Metabolism

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“…Since UCP3 has been implicated in the mechanism of adaptive thermogenesis (Clapham et al, 2000;Lowell & Spiegelman, 2000), the significant increases in the levels of UCP3 and PKA-RIIb in the BAT of adult Ucp1 -/-mice fed the standard diet may indicate enhanced β-adrenergic responsiveness similar to that seen in cold exposure, contributing to thermogenesis and fatty acid metabolism. The thermogenic role of UCP3 is still controversial, but Mills et al (2003) recently indicated in their report based on a study using UCP3-deficient mice that UCP3 was required for the rise in skeletal and core temperature associated with the administration of an amphetamine-type stimulant.…”

Section: Discussionmentioning

confidence: 99%

UCP1 deficiency increases susceptibility to diet‐induced obesity with age

et al. 2005

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SummaryLoss of nonshivering thermogenesis in mice by inactivation of the mitochondrial uncoupling protein gene ( Ucp1 -/-mice) causes increased sensitivity to cold and unexpected resistance to diet-induced obesity at a young age. To clarify the role of UCP1 in body weight regulation throughout life and influence of UCP1 deficiency on longevity, we longitudinally analyzed the phenotypes of Ucp1 -/-mice maintained in a room at 23 °°°° C. There was no difference in body weight and lifespan between genotypes under the standard chow diet condition, whereas the mutant mice developed obesity with age under the high-fat (HF) diet condition. Compared with Ucp1 +/+ mice, Ucp1 -/-mice showed increased expression of genes related to thermogenesis and fatty acid metabolism, such as β β β β 3-adrenergic receptor, in adipose tissues of the 3-month-old mutants; however, the augmented expression was reduced in Ucp1 +/+ mice in 11-month-old Ucp1 -/-mice fed the HF diet. Likewise, the increased levels of UCP3 and cAMPdependent protein kinase in the brown adipose tissue of Ucp1 -/-mice given the standard diet were decreased significantly in that of Ucp1 -/-mice fed the HF diet, which animals showed impaired norepinephrine-induced lipolysis in their adipose tissues. These results suggest profound attenuation of β β β β -adrenergic responsiveness and fatty acid utilization in Ucp1 -/-mice fed the HF diet, bringing them to late-onset obesity. Our findings provide evidence that UCP1 is neither essential for body weight regulation nor for longevity under conditions of standard diet and normal housing temperature, but deficiency increases susceptibility to obesity with age in combination with HF diet.

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“…Mechanisms of MDMA-induced hyperthermia are complex and appear to involve a combination of (1) vasoconstriction (Pedersen & Blessing, 2001) and thermogenesis mediated through the activation of a 1 -adrenoreceptor (a 1 AR) (McDaid & Docherty, 2001;Sprague et al, 2003) and resultant blood pooling, (2) b 3 -adrenoreceptor (b 3 AR) activation resulting in skeletal muscle thermogenesis and (3) activation of the skeletal muscle thermogenic protein, uncoupling protein-3 (UCP3, Mills et al, 2003). We previously observed that the a 1 AR antagonist prazosin, when combined with the b 3 AR antagonist cyanopindolol, prevents hyperthermia induced by MDMA in rodents .…”

Section: Introductionmentioning

confidence: 99%

Attenuation of 3,4‐methylenedioxymethamphetamine (MDMA, Ecstasy)‐induced rhabdomyolysis with α₁‐ plus β₃‐adrenoreceptor antagonists

Sprague

Brutcher

Mills

et al. 2004

British J Pharmacology

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1 Studies were designed to examine the effects of a 1 (a 1 AR)-plus b 3 -adrenoreceptor (b 3 AR) antagonists on 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy)-induced hyperthermia and measures of rhabdomyolysis (creatine kinase (CK)) and renal function (blood urea nitrogen (BUN) and serum creatinine (sCr)) in male Sprague-Dawley rats. 2 MDMA (40 mg kg À1 , s.c.) induced a rapid and robust increase in rectal temperature, which was significantly attenuated by pretreatment with the a 1 AR antagonist prazosin (100 mg kg À1 , i.p.) plus the b 3 AR antagonist SR59230A (5 mg kg À1 , i.p.). 3 CK levels significantly increased (peaking at 4 h) after MDMA treatment and were blocked by the combination of prazosin plus SR59230A. 4 At 4 h after MDMA treatment, BUN and sCr levels were also significantly increased and could be prevented by this combination of a 1 AR-plus b 3 AR-antagonists. 5 The results from this study suggest that a 1 AR and b 3 AR play a critical role in the etiology of MDMA-mediated hyperthermia and subsequent rhabdomyolysis.

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Uncoupling the agony from ecstasy

Cited by 129 publications

References 10 publications

Cold-induced PGC-1α expression modulates muscle glucose uptake through an insulin receptor/Akt-independent, AMPK-dependent pathway

Cold-induced PGC-1α expression modulates muscle glucose uptake through an insulin receptor/Akt-independent, AMPK-dependent pathway

UCP1 deficiency increases susceptibility to diet‐induced obesity with age

Attenuation of 3,4‐methylenedioxymethamphetamine (MDMA, Ecstasy)‐induced rhabdomyolysis with α₁‐ plus β₃‐adrenoreceptor antagonists

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Uncoupling the agony from ecstasy

Cited by 129 publications

References 10 publications

Cold-induced PGC-1α expression modulates muscle glucose uptake through an insulin receptor/Akt-independent, AMPK-dependent pathway

Cold-induced PGC-1α expression modulates muscle glucose uptake through an insulin receptor/Akt-independent, AMPK-dependent pathway

UCP1 deficiency increases susceptibility to diet‐induced obesity with age

Attenuation of 3,4‐methylenedioxymethamphetamine (MDMA, Ecstasy)‐induced rhabdomyolysis with α1‐ plus β3‐adrenoreceptor antagonists

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Product

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Attenuation of 3,4‐methylenedioxymethamphetamine (MDMA, Ecstasy)‐induced rhabdomyolysis with α₁‐ plus β₃‐adrenoreceptor antagonists