adipose tissue
• the increase in body weight at 30 degrees C is due to increased tissue mass of epididymal white adipose tissue and liver
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• brown adipose tissue glucose uptake is lower
• however, glucose uptake in other metabolic organs, including skeletal muscle, liver, and brain, is not different
• alpha-lipoic acid supplementation fails to increase glucose uptake in the brown adipose tissue of mutant mice as it does in controls
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• lipoylation in brown adipose tissue is reduced
• brown adipose tissue glucose uptake is lower
• brown adipose tissue shows reduced glucose oxidation and valine oxidation
• pyruvate dehydrogenase activity in interscapular brown adipose tissue (iBAT), but not white adipose tissue, is lower
• supplementation with alpha-lipoic acid fails to increase lipoylation in the iBAT of old mice, fails to enhance pyruvate dehydrogenase activity in BAT, and fails to increase glucose oxidation in aged BAT as in control
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• norepinephrine-induced iBAT thermogenesis is impaired
• alpha-lipoic acid supplementation does not restore norepinephrine-stimulated BAT thermogenesis in old mutant mice as it does is old controls
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growth/size/body
• mice gain more weight than controls at 30 degrees C but not at ambient temperature of 22 degrees C
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homeostasis/metabolism
• mice exhibit lower whole-body energy expenditure than controls following beta-adrenergic receptor activation
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• oxygen consumption rate in the iBAT is lower than in controls following beta3- adrenergic receptor activation
• the increase in oxygen consumption rate maintained at thermoneutrality (30 degrees C) in response to beta3- adrenergic receptor agonist treatment that is seen in wild-type mice is blunted in mutant mice
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• mice show glucose intolerance in the glucose tolerance test, even at ambient temperature
• however, systemic insulin tolerance and glucose-stimulated insulin secretion are not altered
• alpha-lipoic acid supplementation fails to improve systemic glucose tolerance of aged mutant mice as it does in controls
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• pyruvate dehydrogenase activity in interscapular brown adipose tissue (iBAT), but not white adipose tissue, is lower
• mice chronically treated with beta3-adrenergic receptor agonist to stimulate beige fat biogenesis in the inguinal white adipose tissue show lower pyruvate dehydrogenase activity
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cellular
• brown adipose tissue glucose uptake is lower
• however, glucose uptake in other metabolic organs, including skeletal muscle, liver, and brain, is not different
• alpha-lipoic acid supplementation fails to increase glucose uptake in the brown adipose tissue of mutant mice as it does in controls
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• mitochondrial Complex I and II activities are reduced in brown adipose tissue mitochondria
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