growth/size/body
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• when 8-week-old male mice are fed a high-fat diet (HFD) for 12 weeks, their weekly body weight gain is significantly lower than that of HFD-fed wild-type controls starting at week 2 after HFD feeding
• however, no differences in daily food intake, caloric intake, or water consumption are observed under standard chow (SD) or HFD feeding relative to diet-matched wild-type controls
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homeostasis/metabolism
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• both SD-fed and HFD-fed males show normal free fatty acid (FFA) levels in the liver relative to diet-matched wild-type controls
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• expression analysis of beta-oxidation-related genes suggests that peroxisomal fatty acid beta-oxidation is increased while mitochondrial beta-oxidation and subsequent ketogenesis is decreased under HFD feeding
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• when 8-week-old male mice are fed a high-fat diet (HFD) for 12 weeks, their weekly body weight gain is significantly lower than that of HFD-fed wild-type controls starting at week 2 after HFD feeding
• however, no differences in daily food intake, caloric intake, or water consumption are observed under standard chow (SD) or HFD feeding relative to diet-matched wild-type controls
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• males fail to exhibit a statistically significant increase in plasma glucose levels between SD and HFD feeding, unlike wild-type controls; however, HFD-fed males show lower plasma glucose levels than HFD-fed wild-type controls
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• after a 5-h fast, plasma leptin levels are significantly higher than those in wild-type controls
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• males fail to exhibit a statistically significant increase in plasma LDL cholesterol levels between SD and HFD feeding, unlike wild-type controls; however, HFD-fed males show lower plasma LDL cholesterol than HFD-fed wild-type controls
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• HFD-fed males exhibit significantly lower total plasma cholesterol levels than HFD-fed wild-type controls
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• males fail to exhibit a statistically significant increase in plasma FFA levels between SD and HFD feeding, unlike wild-type controls; however, HFD-fed males show lower plasma FFA levels than HFD-fed wild-type controls
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• males fail to exhibit a statistically significant increase in plasma ALT levels between SD and HFD feeding, unlike wild-type controls; however, HFD-fed males show lower plasma ALT levels than HFD-fed wild-type controls
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• males fail to exhibit a statistically significant increase in plasma amylase levels between SD and HFD feeding, unlike wild-type controls; however, HFD-fed males show lower plasma amylase levels than HFD-fed wild-type controls, suggesting improved pancreatic function
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• in response to insulin injection, the level of Akt phosphorylation at Ser-473 is significantly increased in both liver and skeletal muscle tissue, suggesting improved insulin sensitivity
• males show no increased risk of insulin resistance, as determined by responses in ITT and IPGTT tests and fasting plasma insulin levels
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• after a 5-h fast, plasma adiponectin levels are significantly higher than those in wild-type controls
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• hepatic levels of several glycerophospholipid species -- including phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), and phosphatidylinositol (PI) -- tend to increase, whereas most classes of lysophospholipids (LPLs) tend to decrease under both SD and HFD feeding
• under HFD feeding, all classes of LPLs are lower than those in HFD-fed wild-type controls, suggesting that PLAAT1 functions as a phospholipase A1/A2 in liver
• however, total levels of N-acyl-phosphatidylethanolamine (NAPE, an N-acyltransferase product) and N-acylethanolamine (NAE, derived from NAPE) are similar to those in wild-type controls under both SD and HFD feeding, suggesting that PLAAT1 is not a major N-acyltransferase in liver
• mRNA expression of Plaat3 (phospholipase A and acyltransferase 3) is not significantly increased in liver by HFD feeding relative to the SD-fed group
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• males exhibit a significant increase in plasma phospholipid levels between SD and HFD feeding, similar to wild-type controls; however, HFD-fed males show lower plasma phospholipid levels than HFD-fed wild-type controls
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• HFD-fed males show only a 1.2-fold increase in hepatic triglyceride (TG) levels relative to a 4-fold increase in HFD-fed wild-type controls
• however, liver TG levels are not significantly altered under SD feeding
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• males show a marked reduction of N-acyltransferase activity in skeletal muscle relative to wild-type controls
• in contrast, phospholipase A1/A2 (PLA1/A2) activity is only slightly decreased in skeletal muscle, without reaching statistical significance
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• expression analysis of lipid metabolism-related genes suggests that hepatic lipid biosynthesis is decreased under HFD feeding
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liver/biliary system
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• HFD-fed males show only a 1.2-fold increase in hepatic triglyceride (TG) levels relative to a 4-fold increase in HFD-fed wild-type controls
• however, liver TG levels are not significantly altered under SD feeding
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• HFD-fed males show a significant decrease in actual liver weight relative to HFD-fed wild-type controls
• however, liver weight is normal under SD feeding
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dark liver
(
J:343807
)
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• HFD-fed males exhibit darker livers than HFD-fed wild-type controls
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• HFD-fed males exhibit negligible hepatic lipid accumulation relative to HFD-fed wild-type controls, as indicated by oil red O and H&E staining
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adipose tissue
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• HFD-fed males exhibit normal white adipocyte size and no significant alterations in the infiltration of F4/80+ macrophages or mRNA expression of Adgre1 (encoding F4/80) in WAT relative to HFD-fed wild-type controls
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• HFD-fed males show a significant decrease in total and relative WAT weight relative to HFD-fed wild-type controls
• however, WAT weight is normal under SD feeding
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muscle
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• males show a significant decrease in gastrocnemius weight under both SD and HFD feeding conditions; reduction in gastrocnemius weight is significantly smaller on the HFD than on the SD
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• males show a significant decrease in the total weight of quadriceps, tibialis anterior, gastrocnemius and soleus muscles under both SD and HFD feeding conditions; reduction in total skeletal muscle weight is significantly smaller on the HFD than on the SD
• however, weight of femur (as a representative bone) is normal under both SD and HFD feeding
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cellular
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• expression analysis of beta-oxidation-related genes suggests that peroxisomal fatty acid beta-oxidation is increased while mitochondrial beta-oxidation and subsequent ketogenesis is decreased under HFD feeding
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limbs/digits/tail
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• males show a significant decrease in gastrocnemius weight under both SD and HFD feeding conditions; reduction in gastrocnemius weight is significantly smaller on the HFD than on the SD
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