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Figure 1.

Ovarian Morphology of control and IR/LepRPOMC females.

A-E. Ovarian sections throughout the ovaries of individual control and IR/LepRPOMC females were examined for follicle types shown, n = 13–17. F. Ovarian sections throughout the ovaries of control and IR/LepRPOMC females were examined and the percentage of ovaries lacking either preovulatory follicles or corpora lutea (or both) is shown, n = 13–17. Statistical significance was calculated using Fisher's exact test (p = 0.0481).

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Figure 2.

IR/LepRPOMC females have reduced ovulation but show normal cycling suppression from fasting.

A. Example of delay in resumption of estrous cycles measured by vaginal cytology taken before, during, and after a 48 hour fast. B. Delay from fast quantified for control (white bars) or IR/LepRPOMC (black bars) mice, n = 9–13 (not significant). Mean ± SEM.

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Figure 3.

Increased fat mass and intra-abdominal adipocyte hypertrophy in IR/LepRPOMC mice.

A. Body weight of IR/LepRPOMC female mice and controls. B. Fat and lean mass of IR/LepRPOMC females and controls measured by NMR (white bars = control mice, black bars = IR/LepRPOMC mice), n = 5–6. C. Subcutaneous and intra-abdominal fat volume measured by CT scan in IR/LepRPOMC females and controls, n = 5–6 D. Section of perigonadal fat tissue, paraffin embedded and stained with H/E. Each panels are shown at 200x. E. Adipocyte size calculated from H/E stained perigonadal fat pads, 50 cells counted per section/mouse, n = 15–24 mice. * indicates p<0.05. F. Serum leptin levels of control (white bars) or IR/LepRPOMC (black bars) mice 3 hours after chow removal. n = 4, ** indicates p<0.01. Mean ± SEM.

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Figure 4.

IR/LepRPOMC Females have tissue-specific low-grade inflammation.

A. Immunostaining for macrophage marker F4/80 in adipose tissue. F4/80 staining (FITC) was merged with DAPI to identify activated macrophages. B. Adipose tissue F4/80 gene expression. C. Adipose tissue CD11c gene expression. D. Adipose tissue IL-6 gene expression. E. Adipose tissue IL-1β gene expression. F. Ovary IL-6 gene expression. G. Liver IL-1β gene expression. Mean ± SEM, n = 4–5 * = p<.05 and ** = p<.01 compared with controls.

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Table 1.

Serum inflammatory markers are normal in IR/LepRPOMC Females.

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Figure 5.

IR/LepRPOMC females are hyperglycemic and show hyperglycemia during pregnancy.

A. IR/LepRPOMC female glucose levels under basal conditions (n = 6–7) ** p<0.01. B. Fasted glucose levels in a second cohort of females, before pregnancy and on gestational day 12 and 15 (Black circles are control dams, open triangles are IR/LepRPOMC dams; n = 11–12) * p<0.05, compared with controls at same timepoint; + p<0.05, compared with pre-pregnancy values of same group. C. Glucose tolerance testing (2 g/kg) performed on day 15–18 of gestation. (Black circles are control dams, open triangles are IR/LepRPOMC dams; n = 6). Mean ± SEM.

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