growth/size/body
N |
• females exhibit normal body weight regardless of diet
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• significant reduction in whole-body fat mass in both LFD-fed and HFD-fed males relative to wild-type controls at 18 weeks of age
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• significant reduction in lean body mass in HFD-fed males relative to wild-type controls at 18 weeks of age
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• males fed either a low-fat diet (LFD) or a high-fat diet (HFD) for 16 weeks, beginning at 5 weeks of age, show a significant reduction in body weight (~5 g less) relative to wild-type controls
• however, food intake and total physical activity are normal
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adipose tissue
• markedly reduced weight and size of visceral (eWAT) and subcutaneous (iWAT) fat depots in LFD-fed males relative to wild-type controls
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• significant reduction in whole-body fat mass in both LFD-fed and HFD-fed males relative to wild-type controls at 18 weeks of age
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• markedly reduced weight of eWAT fat depots in LFD-fed males relative to wild-type controls
• however, adipocyte morphology is relatively normal
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• markedly reduced weight of iWAT fat depots in LFD-fed males relative to wild-type controls
|
homeostasis/metabolism
N |
• normal whole-body glucose metabolism in LFD-fed males with no significant differences in glucose or insulin tolerance tests relative to wild-type controls
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• in the fasted state, TG content of very low-density lipoprotein (VLDL) particles is ~1.8-fold greater in LFD-fed males relative to wild-type controls
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• significantly increased plasma FFA levels 15 min post beta3-adrenergic receptor agonist (CL316243) injection in LFD-fed males relative to wild-type controls
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• significantly increased plasma glycerol levels 15 min post beta3-adrenergic receptor agonist (CL316243) injection in LFD-fed males relative to wild-type controls
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• in the fasted state, plasma triglyceride (TG) levels are significantly higher in LFD-fed males relative to wild-type controls; however, no differences in fecal TG content are observed
• dramatic rise in plasma TG levels in LFD-fed males during an oral fat tolerance test (OFTT) at 2 hours after an oral lipid gavage
• significantly increased plasma TG levels in LFD-fed males during an intraperitoneal fat tolerance test
• significantly increased plasma TG levels after administration of poloxamer 407 (an inhibitor of lipoprotein lipase activity) in overnight-fasted mice
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• markedly increased VLDL-TG levels in LFD-fed males relative to wild-type controls
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• significantly increased energy expenditure in both LFD-fed and HFD-fed males relative to wild-type controls at 20 weeks of age; effect is more pronounced in LFD-fed males
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• significantly increased carbon dioxide production rate (VCO2) in HFD-fed males relative to wild-type controls at 20 weeks of age
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• significantly increased oxygen consumption rate (VO2) and fat oxidation in LFD-fed males relative to wild-type controls at 20 weeks of age
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• significantly reduced respiratory exchange ratio (RER) in LFD-fed males relative to wild-type controls at 20 weeks of age
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• significantly reduced cholesterol levels in fecal pellets from LFD-fed males
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• significantly reduced total plasma cholesterol in LFD-fed males relative to wild-type controls
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• cholesterol content is strikingly reduced in HDL particle fractions in LFD-fed males relative to wild-type controls
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• cholesterol content is strikingly reduced in LDL particle fractions in LFD-fed males relative to wild-type controls
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• significantly reduced hepatic cholesterol content in LFD-fed males relative to wild-type controls
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• phosphatidylcholines (PC) and phosphatidylethanolamines (PE) are markedly elevated, indicating increased phospholipid synthesis in the liver of LFD-fed males relative to wild-type controls
• several intermediates of phospholipid metabolism, including CMP, cytidine 5'-diphosphocholine, glycerophosphorylcholine, cytidine 5'-diphosphoethanolamine, and glycerophosphoethanolamine, are increased in the liver
• many diacylglycerols are significantly reduced in the liver, suggesting an increased utilization of these precursors in phospholipid synthesis
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• markedly reduced hepatic TG content in LFD-fed males relative to wild-type controls
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• elevated metabolic rate in LFD-fed males relative to wild-type controls at 20 weeks of age
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• both mRNA and protein expression of 3 lypolytic enzymes (ATGL, HSL, MGL) are significantly upregulated in eWAT but not in liver of LFD-fed males relative to wild-type controls
• strikingly elevated phosphorylation of PKA substrates in eWAT resulting in enhanced adipose tissue lipolysis in LFD-fed males
• elevated in vivo lipolysis in response to beta3-adregenic receptor agonist (CL316243) stimulation in LFD-fed males
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liver/biliary system
• significantly reduced hepatic cholesterol content in LFD-fed males relative to wild-type controls
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• markedly reduced hepatic TG content in LFD-fed males relative to wild-type controls
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small liver
(
J:282612
)
• markedly reduced liver size in LFD-fed males relative to wild-type controls
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• enhanced hepatic VLDL-TG secretion contributing to impaired plasma lipid clearance following acute lipid load
|