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EP3R–/– mice exhibit an obese phenotype with a "night" …


Biology Articles » Chronobiology » Night eating and obesity in the EP3R-deficient mouse » Figures

Figures
- Night eating and obesity in the EP3R-deficient mouse

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Fig. 1. EP3R–/– mice show an increase in body weight that results in an obese phenotype. (A) A male EP3R–/– mouse (Right) and a WT littermate (Left) at 30 weeks of age. (B) Measurement of body weight at different time points shows that overweight becomes significant on EP3R–/– mice after week 12 (t = 3.17; P = 0.048). Evaluation of body weight at different time points shows a consistent increment of body weight in EP3R–/– mice at weeks 16 (t = 5.29; P = 0.0001), 20 (t = 4.41; P = 0.001), 27 (t = 5.97; P = 0.0001), 31 (t = 6.36; P = 0.0001), and 40 (t = 4.7; P = 0.0006). After week 30, weight differences are {approx}30% of the body weight of corresponding WT littermate controls. (C) Early deposition of intraabdominal and subcutaneous fat pads in EP3R–/– mice at 3 months of age becomes an important contributor to body weight gain (t = 3.79; P = 0.0053); at 6 months of age, the contribution becomes higher (t = 18.36; P = 0.0001). (D) At 3 months, intraabdominal fat pads are the main site of fat accumulation in EP3R–/– mice (t = 4.35; P = 0.0024). At 6 months, the intraabdominal fat pads (t = 19.55; P = 0.0001), liver (t = 4.68; P = 0.0016), and subcutaneous fat pads (t = 12.09; P = 0.0001) become important sources of fat deposits in EP3R–/– mice. Asterisks indicate significant differences at each given point. For P values, see above.

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Fig. 2. Endocrine changes in EP3R–/– mice vs. WT littermates at 3 and 6 months of age. (Upper) Plasma insulin levels. (Lower) Plasma leptin levels. Asterisks indicate significant differences at each given point. For P values, see text.

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Fig. 3. EP3R–/– mice showed impaired gluclose tolerance and insulin resistance. (A and B) Glucose-tolerance test. Mice were challenged with 1.5 mg of glucose per gram of body weight, and glucose concentrations were measured before glucose challenge and after 15, 30, 60, 120, and 180 min. (C and D) Percentage of changes from baseline on the ability of insulin to acutely stimulate glucose disposal or clearance by performing an acute insulin challenge in EP3R–/– and WT mice at both ages. (C' and D') The raw correspondent blood glucose values (in milligrams per deciliter) used for C and D. Asterisks indicate significant differences at each given point. For P values, see text.

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Fig. 4. Circadian rhythm profile for WT littermates and EP3R–/– mice. Although diurnal distribution of motor activity follows the light–dark cycle, EP3R–/– mice show bouts of increased activity during the light cycle that are associated with grooming and eating behavior. Those bouts of activity are irregular and better detected during the resting phase (see {bigwedge}). (B) Continuous recording of core body temperature (CBT) and motor activity (MA) during 5 days at normothermic conditions (room temperature was 30°C) confirms that EP3R–/– and WT mice are nocturnal and that they follow the low activity–high resting (light cycle) and high activity–low resting (dark cycle) pattern. (C) Averaged data indicate that EP3R–/– mice have an increase in motor activity characterized by bouts of activity that increases the core body temperature (see arrows). The increase in motor activity is associated with grooming and eating behavior. (D) Cumulative data confirm that EP3R–/– mice are more active during the light period. *, P = 0.032.

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Fig. 5. EP3R–/– mice showed increased food consumption. (A and B) Hourly food-intake events as a function of time (A) and effects of 24 h of fasting in EP3R–/– and WT littermates (B). In A, at 3 months of age (Upper), EP3R–/– mice show an increase in food intake characterized by continuous feeding during the dark period (see arrows), whereas WT littermate controls show a similar increase in feeding followed by a period of temporary decrease and then by a second increase in food consumption in the same period. At 6 months of age (Lower), the increase in feeding in the EP3R–/– mice is extended to the light cycle (see arrows; P values are given in the text). In B, food intake was measured every 12 h. At 3 months of age (Upper), baseline measurement for 3 days confirmed that EP3R–/– mice ate more during the dark period (*, P –/– mice ate more during both light and dark cycles (*, P

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