cardiovascular system
• 52% reduction in cardiac triacylglycerol content, along with a marked reduction of lipid droplets stained by ORO in the heart
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homeostasis/metabolism
• 52% reduction in cardiac triacylglycerol content, along with a marked reduction of lipid droplets stained by ORO in the heart
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• ~11% decrease in whole-body fatty acid oxidation
• however, no significant alterations in fatty acid uptake, fatty acid oxidation or esterification of extracellular-derived fatty acids in isolated skeletal (soleus) muscle under basal or forskolin-stimulated conditions
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• pulse-chase experiments on primary myotubes from skeletal muscle show that oxidation of triacylglycerol-derived fatty acids is increased concomitant with increased depletion of the 14C labeled triacylglycerol, indicating degradation of triacylglycerol in skeletal muscle
• however, mitochondrial content and function are not enhanced in either isolated myotubes or intact skeletal muscle
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• respiratory exchange ratio is increased, as assessed by indirect calorimetry
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• glucose tolerance is improved on a low-fat diet (LFD), as shown by an attenuated blood glucose excursion after glucose administration
• glucose tolerance is markedly enhanced on a high-fat diet (HFD), with HFD-fed mice showing comparable glucose tolerance to LFD-fed wild-type mice
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• skeletal muscle glycogen content is reduced following hyperinsulinemic euglycemic clamp
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• both hepatic glucose production and insulin sensitive gluconeogenic gene expression are reduced during insulin clamp conditions, suggesting improved hepatic insulin sensitivity
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• mice become insulin resistant due to reduced insulin stimulated glucose disposal in skeletal muscle and adipose tissue, but maintain insulin sensitivity in the liver
• reduced skeletal muscle insulin sensitivity, observed during hyperinsulinemic euglycemic clamps, is associated with ceramide accumulation
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• sphingomyelin levels are increased in cultured myotubes
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• ceramide level is increased by 53% in skeletal muscle, whereas diacylglycerol levels remains normal
• ceramide, dihydro- and hexosyl-ceramide levels are increased in cultured myotubes, whereas other lipid types such as phospholipids and sterols are mostly normal
• however, no evidence of ER stress, inflammation or oxidative stress in skeletal muscle
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• significant reduction of triacylglycerol content in red quadriceps (oxidative) skeletal muscle
• however, no significant alterations in mixed quadriceps or liver triacylglycerol content
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• ~11% increase in whole-body carbohydrate oxidation
• however, no significant alteration in glucose oxidation in isolated skeletal (soleus) muscle
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• 24 h fasted mice fail to show lipid droplet staining in skeletal muscle, indicating increased intramyocelluar lipolysis and an inability to expand the intramyocellular triacylglycerol pool
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muscle
• 52% reduction in cardiac triacylglycerol content, along with a marked reduction of lipid droplets stained by ORO in the heart
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• skeletal muscle glycogen content is reduced following hyperinsulinemic euglycemic clamp
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• significant reduction of triacylglycerol content in red quadriceps (oxidative) skeletal muscle
• however, no significant alterations in mixed quadriceps or liver triacylglycerol content
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adipose tissue
• glucose uptake is reduced in white adipose tissue
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cellular
• glucose uptake is reduced in white adipose tissue
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• ~11% decrease in whole-body fatty acid oxidation
• however, no significant alterations in fatty acid uptake, fatty acid oxidation or esterification of extracellular-derived fatty acids in isolated skeletal (soleus) muscle under basal or forskolin-stimulated conditions
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• pulse-chase experiments on primary myotubes from skeletal muscle show that oxidation of triacylglycerol-derived fatty acids is increased concomitant with increased depletion of the 14C labeled triacylglycerol, indicating degradation of triacylglycerol in skeletal muscle
• however, mitochondrial content and function are not enhanced in either isolated myotubes or intact skeletal muscle
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