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Table 1.

Comparison of dietary fat and energy composition between the standard and high fat diets.

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Figure 1.

Obesity and adiposity in male and female high fat fed 3xTg-AD mice.

A, Body weight in male and female 3xTg-AD mice across the 4 month feeding period. B, Percent change in body weight relative to baseline weight after 4 months of feeding with either standard or high fat diet. C, Abdominal retroperitoneal fat pad weight in male (solid bars) and female (open bars) 3xTg-AD mice. D, Representative images of hematoxylin-stained livers in male and female mice fed regular and high fat diets. E, Quantification of microvesicular (<15 µm) and macrovesicular (>15 µm) fat accumulation in liver. F. Serum testosterone and estradiol levels in male and female mice respectively. Data presented as mean ± SEM.† p<0.001 relative to matched time point males fed regular diet. ‡p<0.001 relative to matched time point females with regular diet. **p<0.001 relative to regular diet fed mice. *p<0.01 male versus female mice. γp<0.05 relative to sex-matched regular diet fed mice.

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Figure 2.

Elevated fasting blood glucose and insulin levels in high fat fed male but not female 3xTg-AD mice.

A, Fasting blood glucose concentrations in male and female 3xTg-AD mice across the 4 month feeding period. B, Fasting insulin concentrations in male (solid bars) and female (open bars) 3xTg-AD mice after 4 months of feeding with either standard or high fat diet. C, Insulin resistance index, HOMA-IR. Data presented as mean ± SEM. *p<0.001 relative to standard diet group at the matched sex and time point; † p<0.001 relative to matched sex standard diet group.

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Figure 3.

Ovarian hormones protect high fat fed female mice against hyperglycemia.

A, Body weight in female 3xTg-AD mice was not affected by ovariectomy (OVX) in either standard or high fat groups. B, High fat diet increased abdominal retroperitoneal fat pad weight in sham-operated (solid bars) and ovariectomised (open bars) female 3xTg-AD mice equally. C, High fat diet increased fasting glucose concentrations in high fat fed female 3xTg-AD mice following ovariectomy D, Fasting insulin concentrations in sham-operated (solid bars) and ovariectomised (open bars) female 3xTg-AD mice after 4 months of feeding with either standard or high fat diet. C, Insulin resistance index, HOMA-IR. Data presented as mean ± SEM. *p<0.001 relative to regular diet fed mice; † p<0.001 relative to all other groups.

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Figure 4.

Impaired behavioral deficits in high fat fed 3xTg-AD mice.

A, Spontaneous alternation behavior (SAB) in the Y-maze in standard and high fat fed male and female 3xTg-AD mice. B, Object recognition performance in standard and high fat fed female 3xTg-AD mice at 2 and 18 hrs after training (2 and 18 hr probe). *p<0.001 relative to matched sex with standard diet. Data presented as mean ± SEM. *p<0.001 relative to matched sex with standard diet. † p<0.001 relative to matched probe trial.

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Figure 4 Expand

Figure 5.

High fat diet increases Aβ accumulation in the hippocampus of male and female 3xTg-AD mice.

A, Hippocampus CA1 Aβ immunoreactivity load values. B–E, Representative photomicrographs show Aβ immunoreactivity in the hippocampus CA1 regions in standard diet fed male (B) and female (C) 3xTg-AD mice, and high fat fed male (D) and female (E) 3xTg-AD mice. F, Subiculum Aβ immunoreactivity load values. G–J, Representative photomicrographs show Aβ immunoreactivity in the subiculum regions in standard diet fed male (G) and female (H) 3xTg-AD mice, and high fat fed male (I) and female (J) 3xTg-AD mice. Data presented as means ± SEM. *p<0.05 compared to all other groups. *p<0.001 relative to matched sex with standard diet.

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