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Figure 1.

Body weight and calorie intake in the four study groups.

A) Body weight evolution from 4 weeks to 28 weeks old. Animals were started on the HFD at 4 weeks. Arrows indicate weeks 17 and 28, the age when experiments were done (n = 150 animals from 26 litters). B) Body weight of offspring from the four different groups at 17 weeks (Control n = 46 animals from 8 litters, BPA n = 28 from 5 litters, HFD n = 38 from 8 litters and HFD-BPA n = 30 from 5 litters). C) Body weight of offspring from the four different groups at 28 weeks (Control n = 19 animals from 8 litters, BPA n = 15 from 5 litters, HFD n = 26 from 8 litters and HFD-BPA n = 15 from 5 litters), *P<0.01 Student's t-test compared to Control. D) Food intake for the four different groups compared at 17 weeks old (n = 142 animals from 26 litters) E) Food intake for the four different groups compared at 28 weeks old (n = 75 animals from 26 litters). Data are expressed as mean±SEM. Significance by one way ANOVA followed by Tukey, Holm-sidak or Dann's method, p<0.05. b compares control vs. HFD, c control vs. HFD-BPA, d HFD vs. BPA, e HFD vs. HFD-BPA, f BPA vs. HFD-BPA.

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Figure 2.

Adipose tissue weight and plasma NEFA levels in offspring.

A) Perigonadal and B) Retroperitoneal fat depots, expressed as % of body weight at 17 weeks old (n = 8 animals from 5–8 litters). C) Perigonadal and D) Retroperitoneal fat depots, expressed as % of body weight at 28 weeks old. (n = 6–8 animals from 5–8 litters). E) Plasma Nonesterified fatty acids (NEFAs) levels at 17 weeks old (n = 7–9 animals from 7 litters) and F) 28 weeks old (n≥5 animals from 4–7 litters). Data are expressed in mean ±SEM; significance p<0.05 by one way ANOVA followed by Holm-Sidak or Dunnett's method; a control vs. BPA; b control vs. HFD, c control vs. HFD-BPA, d HFD vs. BPA, e HFD vs. HFD-BPA, f BPA vs. HFD-BPA.

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Figure 3.

BPA, HFD and HFD-BPA groups exhibit hyperglycaemia and glucose intolerance.

A) ipGTT were performed on the four groups at 17 weeks old. The inset shows mean±SEM of the ipGTT Area Under the Curve (n≥6 animals from ≥6 litters). B) ipITT in 17 week old animals (n≥6 animals from ≥6 litters) C) ipGTT were performed on the four groups at 28 weeks old. The inset shows mean±SEM of the ipGTT Area Under the Curve (n≥12 animals from ≥6 litters). D) ipITT in 28 week old animal. (n≥11 animals from ≥6 litters). Data are expressed in mean±SEM. Significance P<0.05 by one way ANOVA followed by Tukey or Dunnett's method; a control vs. BPA; b control vs. HFD, c control vs. HFD-BPA, d HFD vs. BPA, e HFD vs. HFD-BPA, f BPA vs. HFD-BPA.

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Table 1.

Plasma hormones and metabolite levels in offspring at the age of 17 weeks.

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Table 2.

Plasma hormones and metabolite levels in 28 week old offspring.

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Figure 4.

Glucose-induced insulin secretion from isolated islets.

A) Insulin secretion from islets exposed to 3, 8 and 16 mM glucose for 1 hour, in animals from the four different groups at the age of 17 weeks. (n≥9 experiments with 7 animals from 7 litters). The inset shows the insulin release when islets were exposed to 3 mM of glucose. B) Insulin secretion from islets exposed to 3, 8 and 16 mM of glucose for 1 hour, in animals from the four different groups at the age of 28 weeks (n≥6 experiments with ≥6 animals from ≥6 litters). C) Insulin content from isolated islets at the age of 17 weeks (n≥10 experiments with 7 animals from 7 litters). D) Insulin content from isolated islets at 28 weeks (n≥8 experiments with ≥6 animals from ≥6 litters). Data are expressed in mean±SEM, p<0.05 by one way ANOVA followed by Tukey, Dunnet or Dunn's method; a control vs. BPA; b control vs. HFD, c control vs. HFD-BPA, d HFD vs. BPA, e HFD vs. HFD-BPA, f BPA vs. HFD-BPA.

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Figure 5.

mRNA gene expression associated with A) Lipogenesis, B) Fatty Acid Uptake, C) Fatty Acid Oxidation and D) Glucose Uptake and Metabolism, in White Adipose Tissue (WAT) from Control (n≥5 animals from ≥5 litters), BPA (n≥5 animals from ≥5 litters), HFD (n≥5animals from ≥5 litters) and HFD-BPA (n≥5 animals from ≥5 litters) dams at 17 weeks old.

Animals were treated with HFD at week 4. Gene expression was assessed by real-time RT-PCR. Data are expressed as mean±SEM and statistical significance was determined using one way ANOVA followed by Tukey, Duncans or Dunn's method. Significance p<0.05; a compared control vs. BPA; b control vs. HFD, c control vs. HFD-BPA, d HFD vs. BPA, e HFD vs. HFD-BPA, f BPA vs. HFD-BPA.

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Figure 6.

mRNA gene expression associated with A) Lipogenesis, B) Fatty Acid and Glucose Uptake, C) Fatty Acid Oxidation and D) Glucose Metabolism, in the liver from Control (n≥5animals from ≥5 litters), BPA (n≥5 animals from ≥5 litters), HFD (n≥5 animals from ≥5 litters) and HFD-BPA (n≥5 animals from ≥5 litters) dams at the age of 17 weeks.

Animals started to be treated with HFD at the age of 4 weeks. Gene expression was assessed by real-time RT-PCR. E) Hepatic trygliceride content from Control (n≥5animals from ≥5 litters), BPA (n≥5 animals from ≥5 litters), HFD (n≥5 animals from ≥5 litters) and HFD-BPA (n≥5 animals from ≥5 litters) dams at the age of 17 weeks. Data are expressed as mean±SEM and statistical significance was determined using one way ANOVA followed by Tukey or Dunn's method. Significance p<0.05; a compares control vs. BPA; b control vs. HFD, c control vs. HFD-BPA, d HFD vs. BPA, e HFD vs. HFD-BPA, f BPA vs. HFD-BPA.

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Figure 7.

mRNA gene expression associated with A) Fatty Acid Oxidation and B) Fatty Acid and Glucose Uptake and Metabolism, in Skeletal Muscle from Control (n≥5 animals from ≥5 litters), BPA (n≥5 animals from ≥5 litters), HFD (n≥5 animals from ≥5 litters) and HFD-BPA (n≥5 animals from ≥5 litters) dams at the age of 17 weeks.

Animals started to be treated with HFD at week 4. Gene expression was assessed by real-time RT-PCR. Data are expressed as mean±SEM and statistical significance was determined using one way ANOVA followed by Duncan or Dunn's method. Significance p<0.05; a compared control vs. BPA; b control vs. HFD, c control vs. HFD-BPA, d HFD vs. BPA, e HFD vs. HFD-BPA, f BPA vs. HFD-BPA.

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