homeostasis/metabolism
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• mice fed a high-fat diet (HFD) for 8 weeks show a significant increase in body weight gain at thermoneutrality (30 degrees C) relative to thermoneutral-housed HFD-fed controls
• however, food intake is not significantly altered in HFD-fed mice at thermoneutrality
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• upon acute cold challenge, lean mice show cold sensitivity (lower rectal temperatures) relative to similarly challenged controls
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• HFD-fed mice exhibit significantly higher blood glucose levels after a 16-hour fast
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• HFD-fed mice exhibit significantly higher serum insulin levels than HFD-fed controls
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• HFD-fed mice exhibit significantly higher serum free fatty acid levels than HFD-fed controls
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• HFD-fed mice show limited capacity to increase whole-body oxygen consumption in response to stimulation with the beta3-adrenergic agonist CL316,243 under thermoneutral conditions
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• HFD-fed mice show significantly decreased whole-body oxygen consumption rates under thermoneutral conditions with no changes in food intake
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• HFD-fed mice exhibit significantly higher blood glucose levels at different time points after intraperitoneal injection of glucose, indicating glucose intolerance
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cellular
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• mitochondria isolated from the iBAT of HFD-fed mice exhibit significantly lower oxygen consumption rates after sequential addition of GDP, oligomycin, and FCCP, with almost no response to FCCP (an uncoupling agent), suggesting that mitochondrial spare and adaptive capacity is highly limited in iBAT
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• TEM images from HFD-fed mice show alterations in mitochondrial ultrastructure
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• HFD-fed mice show a significant reduction in mitochondrial cristae density
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• HFD-fed mice show significant decreases in the steady-state protein levels of the mitochondrial import receptor TOM70 as well as in multiple carriers and reported substrates such as ANT2, SLC25A44, UCP1 and MIC19
• in an in vitro assay, incubation of 35S-TOM70 with mitochondria isolated from the iBAT of HFD-fed mice shows a significant reduction in TOM70 insertion into the outer mitochondrial membrane (OMM)
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adipose tissue
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• HFD-fed mice show significant enlargement of interscapular brown adipose tissue (iBAT)
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• HFD-fed mice exhibit a significant increase in adiposity, as detected by MRI analysis
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• HFD-fed mice show a significant increase in interscapular brown adipose tissue (iBAT) weight
• however, liver weight is not significantly changed in HFD-fed mice
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• H&E staining indicates whitening of iBAT tissue with larger lipid droplets in HFD-fed mice
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• HFD-fed mice show a significant increase in inguinal white adipose tissue (iWAT) weight
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• mitochondria isolated from the iBAT of HFD-fed mice exhibit significantly lower oxygen consumption rates after sequential addition of GDP, oligomycin, and FCCP, with almost no response to FCCP (an uncoupling agent), suggesting that mitochondrial spare and adaptive capacity is highly limited in iBAT
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growth/size/body
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• mice fed a high-fat diet (HFD) for 8 weeks show a significant increase in body weight gain at thermoneutrality (30 degrees C) relative to thermoneutral-housed HFD-fed controls
• however, food intake is not significantly altered in HFD-fed mice at thermoneutrality
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