adipose tissue
• HFD-fed mice show a significant increase in average adipocyte number in BAT relative to HFD-fed wild-type controls
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• HFD-fed mice show a 70% reduction in average adipocyte size in BAT relative to HFD-fed wild-type controls
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• in vitro, differentiation of isolated ear mesenchymal stem cells (EMSCs) into adipocytes is significantly lower than in wild-type controls after 3, 5, and 7 days of culture in differentiation medium
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• after HFD challenge, the epididymal WAT to body weight ratio is significantly lower than in HFD-fed wild-type controls
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• after HFD challenge, the mesenteric WAT to body weight ratio is significantly lower than in HFD-fed wild-type controls
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• after 14 weeks of HFD feeding, adipose tissue fibrosis is reduced to 29% and 25% in epididymal WAT and mesenteric WAT, respectively; mRNA levels of fibrosis-related genes are significantly lower in epididymal WAT relative to those in HFD-fed wild-type controls
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• after HFD challenge, the subcutaneous WAT to body weight ratio is significantly lower than in HFD-fed wild-type controls
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• after 14 weeks of HFD feeding, average adipocyte area is reduced by 27% in epididymal WAT and by 38% in subcutaneous WAT
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• HFD-fed mice show significantly higher UCP1 protein levels along with increased mRNA levels of lipid catabolism and thermogenesis-related genes in BAT
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• after 14 weeks of HFD feeding, activation of the NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome is inhibited in WAT, resulting in decreased cleavage of caspase-1 in epididymal WAT and lower serum IL-1beta and IL-18 levels
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homeostasis/metabolism
• HFD-fed mice exhibit a significantly lower level of serum leptin than HFD-fed wild-type controls
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• HFD-fed mice exhibit a significantly lower serum total cholesterol level than HFD-fed wild-type controls
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• HFD-fed mice exhibit a significantly lower serum low-density lipoprotein cholesterol (LDL-C) level than HFD-fed wild-type controls
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• HFD-fed mice exhibit a significantly lower serum TG level than HFD-fed wild-type controls
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• after 14 weeks of HFD feeding, serum IL-1beta levels are significantly lower than in HFD-fed wild-type controls
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• after 14 weeks of HFD feeding, serum IL-18 levels are significantly lower than in HFD-fed wild-type controls
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• HFD-fed mice exhibit a significantly higher energy expenditure at night during a 48-h period than HFD-fed wild-type controls
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• when fed a high-fat diet (HFD) for 14 weeks, 7- to 8-week-old male mice gain significantly less body weight starting from 6 weeks and show significantly decreased body weight and fat mass after 14 weeks of HFD feeding; the ratios of epididymal WAT, subcutaneous WAT, and mesenteric WAT to body weight are significantly lower than in HFD-fed wild-type controls
• however, food intake is normal under HFD conditions and no differences in body weight or WAT histology are observed under normal diet (ND) conditions
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• HFD-fed mice exhibit a significantly higher oxygen consumption at night during a 48-h period than HFD-fed wild-type controls
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• after 14 weeks of HFD feeding, both male and female mice show increased glucose tolerance relative to HFD-fed wild-type controls
• however, no differences in glucose tolerance are noted after 4 weeks of HFD feeding when body weight is normal
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• after 14 weeks of HFD feeding, both male and female mice show increased insulin sensitivity relative to HFD-fed wild-type controls
• however, no differences in insulin sensitivity are noted after 4 weeks of HFD feeding when body weight is normal
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• HFD-fed mice exhibit a significantly higher level of serum adiponectin than HFD-fed wild-type controls
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• HFD-fed mice exhibit a significantly lower liver TG content than HFD-fed wild-type controls
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• after 14 weeks of HFD feeding, mice exhibit significantly lower mRNA levels of de novo lipogenesis genes in the liver relative to HFD-fed wild-type controls
• however, hepatic expression of fatty acid beta-oxidation genes is normal
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liver/biliary system
• HFD-fed mice exhibit a significantly lower liver TG content than HFD-fed wild-type controls
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• HFD-fed mice exhibit a significantly lower liver weight and liver weight/body weight ratio than HFD-fed wild-type controls
• however, liver weight is normal under ND conditions
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• after 14 weeks of HFD feeding, mice exhibit a significantly lower liver weight and triglyceride (TG) content and smaller liver lipid droplets than HFD-fed wild-type controls, with a 2.7-fold increase in small-sized droplets and an 81% decrease in large-sized droplets seen in male mice
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immune system
• after only 4 weeks of HFD feeding (when body weight is normal), the number of adipose tissue macrophages (CD11b+/F4/80+) and proinflammatory macrophages (CD11b+/F4/80+/CD11c+) is significantly decreased in epididymal WAT
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• after 14 weeks of HFD feeding, serum IL-1beta levels are significantly lower than in HFD-fed wild-type controls
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• after 14 weeks of HFD feeding, serum IL-18 levels are significantly lower than in HFD-fed wild-type controls
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• after 14 weeks of HFD feeding, male mice show strong resistance to macrophage infiltration in WAT, with significantly reduced mRNA levels of macrophage markers CD68 and F4/80; the number of crown-like structures, composed of macrophages surrounding dead or dying adipocytes, is decreased by 92% in both epididymal and subcutaneous WAT
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behavior/neurological
• HFD-fed mice exhibit a significantly higher total locomotor activity/BW on either day or night than HFD-fed wild-type controls
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integument
• after HFD challenge, the subcutaneous WAT to body weight ratio is significantly lower than in HFD-fed wild-type controls
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growth/size/body
• when fed a high-fat diet (HFD) for 14 weeks, 7- to 8-week-old male mice gain significantly less body weight starting from 6 weeks and show significantly decreased body weight and fat mass after 14 weeks of HFD feeding; the ratios of epididymal WAT, subcutaneous WAT, and mesenteric WAT to body weight are significantly lower than in HFD-fed wild-type controls
• however, food intake is normal under HFD conditions and no differences in body weight or WAT histology are observed under normal diet (ND) conditions
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cellular
• in vitro, differentiation of isolated ear mesenchymal stem cells (EMSCs) into adipocytes is significantly lower than in wild-type controls after 3, 5, and 7 days of culture in differentiation medium
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hematopoietic system
• after only 4 weeks of HFD feeding (when body weight is normal), the number of adipose tissue macrophages (CD11b+/F4/80+) and proinflammatory macrophages (CD11b+/F4/80+/CD11c+) is significantly decreased in epididymal WAT
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