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Higher core body temperature, metabolic rate and lipolysis in BAT of Cidea-null (-/-) mice relative to wild-type (+/+) mice.(a) Core body temperature in 4-week-old wild-type and Cidea-null mice of 129 inbred background. Time point -1 was before fasting and before cold exposure; time point 0 was after fasting and before cold exposure. Data shown are mean + s.e.m. of five mice in each group. * P < 0.05. (b) Whole-body oxygen consumption rate, represented by mean s.e.m. of VO2 for 12 mice in each group (left). Mean s.e.m. of RER (VCO2/VO2) for 12 fasting mice in each group (right). * P < 0.05, *** P < 0.001. (c−h) Images of transmission electron microscopy of BAT of wild-type (c,e,g) and Cidea-null mice (d,f,h) at 1 month (c−f) and 9 months (g,h) of age. Scale bars = 2 m. RT, room temperature. (i) Percentage of lipid volume in BAT of 4-week-old wild-type and Cidea-null mice before (room temperature; RT) and after cold exposure. Three male mice were tested in each group. ** P < 0.01. (j,k) Greater lipolysis in BAT of Cidea-null mice. Seven male mice 5−6 weeks old were used in the test. *** P < 0.001.

Higher core body temperature, metabolic rate and lipolysis in BAT of Cidea-null (-/-) mice relative to wild-type (+/+) mice.(a) Core body temperature in 4-week-old wild-type and Cidea-null mice of 129 inbred background. Time point -1 was before fasting and before cold exposure; time point 0 was after fasting and before cold exposure. Data shown are mean + s.e.m. of five mice in each group. * P < 0.05. (b) Whole-body oxygen consumption rate, represented by mean s.e.m. of VO2 for 12 mice in each group (left). Mean s.e.m. of RER (VCO2/VO2) for 12 fasting mice in each group (right). * P < 0.05, *** P < 0.001. (c−h) Images of transmission electron microscopy of BAT of wild-type (c,e,g) and Cidea-null mice (d,f,h) at 1 month (c−f) and 9 months (g,h) of age. Scale bars = 2 m. RT, room temperature. (i) Percentage of lipid volume in BAT of 4-week-old wild-type and Cidea-null mice before (room temperature; RT) and after cold exposure. Three male mice were tested in each group. ** P < 0.01. (j,k) Greater lipolysis in BAT of Cidea-null mice. Seven male mice 5−6 weeks old were used in the test. *** P < 0.001.

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The thermogenic activity of brown adipose tissue (BAT), important for adaptive thermogenesis and energy expenditure, is mediated by the mitochondrial uncoupling protein1 (Ucp1) that uncouples ATP generation and dissipates the energy as heat. We show here that Cidea, a protein of unknown function sharing sequence similarity with the N-terminal regio...

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... maintained at room temperature, brown adipocytes of one- month-old wild-type and Cidea-null mice contained lipid droplets of similar size (Fig. 3c,d), but after overnight exposure to cold, brown adipocytes of Cidea-null mice had almost no lipid droplets left (Fig. 3e,f). Quantitative analysis of lipid volume density showed that lipid volume in brown adipocytes of wild-type mice exposed to cold (4 °C) overnight decreased from 25% to 12% mice (Fig. ...
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... maintained at room temperature, brown adipocytes of one- month-old wild-type and Cidea-null mice contained lipid droplets of similar size (Fig. 3c,d), but after overnight exposure to cold, brown adipocytes of Cidea-null mice had almost no lipid droplets left (Fig. 3e,f). Quantitative analysis of lipid volume density showed that lipid volume in brown adipocytes of wild-type mice exposed to cold (4 °C) overnight decreased from 25% to 12% mice (Fig. ...
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... maintained at room temperature, brown adipocytes of one- month-old wild-type and Cidea-null mice contained lipid droplets of similar size (Fig. 3c,d), but after overnight exposure to cold, brown adipocytes of Cidea-null mice had almost no lipid droplets left (Fig. 3e,f). Quantitative analysis of lipid volume density showed that lipid volume in brown adipocytes of wild-type mice exposed to cold (4 °C) overnight decreased from 25% to 12% mice (Fig. ...
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... Cidea was predominantly expressed in BAT, we assessed the effect of Cidea deficiency on thermoregulation and metabolism. When exposed to cold for 1 h, Cidea-null male mice had core body temperatures that were 0.6 °C (P < 0.05) higher than those of wild- type mice (Fig. 3a). Overall, both male and female Cidea-null mice had significantly higher core body temperatures than wild-type mice (two-tailed paired t-test, P < 0.01). We assessed the effect of Cidea disruption on whole-body metabolic rates by measuring oxygen consumption and respiratory exchange rate (RER) with indirect calorimetry. Total oxygen consumption rate was 10% higher in Cidea-null mice (P < 0.0001, Fig. 3b) than in wild-type mice. RER, calculated as the ratio of VCO 2 and VO 2 , was slightly lower (0.7294 ± 0.003427 versus 0.7207 ± 0.002524; P < 0.05; Fig. 3b) in Cidea-null mice than in wild-type mice, indicating a higher percentage of lipid metabolism in the mutant mice. The increase in body temperature and metabolism in Cidea-null mice suggests that Cidea has an impor- tant role in regulating energy ...
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... Cidea was predominantly expressed in BAT, we assessed the effect of Cidea deficiency on thermoregulation and metabolism. When exposed to cold for 1 h, Cidea-null male mice had core body temperatures that were 0.6 °C (P < 0.05) higher than those of wild- type mice (Fig. 3a). Overall, both male and female Cidea-null mice had significantly higher core body temperatures than wild-type mice (two-tailed paired t-test, P < 0.01). We assessed the effect of Cidea disruption on whole-body metabolic rates by measuring oxygen consumption and respiratory exchange rate (RER) with indirect calorimetry. Total oxygen consumption rate was 10% higher in Cidea-null mice (P < 0.0001, Fig. 3b) than in wild-type mice. RER, calculated as the ratio of VCO 2 and VO 2 , was slightly lower (0.7294 ± 0.003427 versus 0.7207 ± 0.002524; P < 0.05; Fig. 3b) in Cidea-null mice than in wild-type mice, indicating a higher percentage of lipid metabolism in the mutant mice. The increase in body temperature and metabolism in Cidea-null mice suggests that Cidea has an impor- tant role in regulating energy ...
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... Cidea was predominantly expressed in BAT, we assessed the effect of Cidea deficiency on thermoregulation and metabolism. When exposed to cold for 1 h, Cidea-null male mice had core body temperatures that were 0.6 °C (P < 0.05) higher than those of wild- type mice (Fig. 3a). Overall, both male and female Cidea-null mice had significantly higher core body temperatures than wild-type mice (two-tailed paired t-test, P < 0.01). We assessed the effect of Cidea disruption on whole-body metabolic rates by measuring oxygen consumption and respiratory exchange rate (RER) with indirect calorimetry. Total oxygen consumption rate was 10% higher in Cidea-null mice (P < 0.0001, Fig. 3b) than in wild-type mice. RER, calculated as the ratio of VCO 2 and VO 2 , was slightly lower (0.7294 ± 0.003427 versus 0.7207 ± 0.002524; P < 0.05; Fig. 3b) in Cidea-null mice than in wild-type mice, indicating a higher percentage of lipid metabolism in the mutant mice. The increase in body temperature and metabolism in Cidea-null mice suggests that Cidea has an impor- tant role in regulating energy ...
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... volume density in brown adipocytes of Cidea-null mice decreased from 23% to less than 2% (Fig. 3i), indicating that ...
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... confirm that lipolysis in BAT is enhanced in Cidea-null mice, we determined the amounts of glycerol and FFA released from explants of BAT and WAT that were maintained in vitro. The amount of glyc- erol released from BAT of Cidea-null mice was 67% higher than that of wild-type mice (0.5830 ± 0.01580 versus 0.9743 ± 0.03228 µmol g -1 h -1 ) at basal level and 198% higher than that of wild-type mice (1.824 ± 0.05541 versus 5.440 ± 0.1473 µmol g -1 h -1 ) in the presence of isoproterenol (Fig. 3j), suggesting enhanced lipolysis. The amount of non-esterified fatty acids (NEFA) released from BAT of Cidea-null mice was lower in both basal and isoproterenol-treated tissue relative to that of wild-type mice (Fig. 3j). As the complete lipolysis of 1 mol of triacylglycerides yields 1 mol of glycerol and 3 mol of fatty acids, the lower levels of fatty acid released from BAT suggest that Cidea- null mice may have increased fatty acid recycling or fatty acid oxida- tion. On the contrary, no difference in the release of glycerol or NEFA was observed in WAT from wild-type and Cidea-null mice (Fig. ...
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... confirm that lipolysis in BAT is enhanced in Cidea-null mice, we determined the amounts of glycerol and FFA released from explants of BAT and WAT that were maintained in vitro. The amount of glyc- erol released from BAT of Cidea-null mice was 67% higher than that of wild-type mice (0.5830 ± 0.01580 versus 0.9743 ± 0.03228 µmol g -1 h -1 ) at basal level and 198% higher than that of wild-type mice (1.824 ± 0.05541 versus 5.440 ± 0.1473 µmol g -1 h -1 ) in the presence of isoproterenol (Fig. 3j), suggesting enhanced lipolysis. The amount of non-esterified fatty acids (NEFA) released from BAT of Cidea-null mice was lower in both basal and isoproterenol-treated tissue relative to that of wild-type mice (Fig. 3j). As the complete lipolysis of 1 mol of triacylglycerides yields 1 mol of glycerol and 3 mol of fatty acids, the lower levels of fatty acid released from BAT suggest that Cidea- null mice may have increased fatty acid recycling or fatty acid oxida- tion. On the contrary, no difference in the release of glycerol or NEFA was observed in WAT from wild-type and Cidea-null mice (Fig. ...
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... confirm that lipolysis in BAT is enhanced in Cidea-null mice, we determined the amounts of glycerol and FFA released from explants of BAT and WAT that were maintained in vitro. The amount of glyc- erol released from BAT of Cidea-null mice was 67% higher than that of wild-type mice (0.5830 ± 0.01580 versus 0.9743 ± 0.03228 µmol g -1 h -1 ) at basal level and 198% higher than that of wild-type mice (1.824 ± 0.05541 versus 5.440 ± 0.1473 µmol g -1 h -1 ) in the presence of isoproterenol (Fig. 3j), suggesting enhanced lipolysis. The amount of non-esterified fatty acids (NEFA) released from BAT of Cidea-null mice was lower in both basal and isoproterenol-treated tissue relative to that of wild-type mice (Fig. 3j). As the complete lipolysis of 1 mol of triacylglycerides yields 1 mol of glycerol and 3 mol of fatty acids, the lower levels of fatty acid released from BAT suggest that Cidea- null mice may have increased fatty acid recycling or fatty acid oxida- tion. On the contrary, no difference in the release of glycerol or NEFA was observed in WAT from wild-type and Cidea-null mice (Fig. ...
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... mice catabolized lipids in BAT at a higher rate. After we removed the mice from the cold and allowed them to recover at room temper- ature for 1 week, brown adipocytes from wild-type and Cidea-null mice had similar amounts of lipid accumulation (data not shown). However, decreased lipid accumulation in brown adipocytes was clearly evident in adult aged Cidea null mice as compared with wild- type. Brown adipocytes from nine-month-old wild-type mice con- tained large lipid droplets that closely resembled those in white adipocytes (Fig. 3g), but those from Cidea-null mice of the same age contained fewer lipid droplets (Fig. 3h). In accordance with the lesser lipid content, the weight of the BAT from nine-month-old Cidea-null mice was 60% less than that of the wild-type mice (data not shown). The rapid depletion of lipid and decrease in fat accumu- lation in BAT were not due to greater lipase activity, as we detected no difference in hormone-sensitive lipase (HSL) activity between BAT from Cidea-null and wild-type mice ( Table ...
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... mice catabolized lipids in BAT at a higher rate. After we removed the mice from the cold and allowed them to recover at room temper- ature for 1 week, brown adipocytes from wild-type and Cidea-null mice had similar amounts of lipid accumulation (data not shown). However, decreased lipid accumulation in brown adipocytes was clearly evident in adult aged Cidea null mice as compared with wild- type. Brown adipocytes from nine-month-old wild-type mice con- tained large lipid droplets that closely resembled those in white adipocytes (Fig. 3g), but those from Cidea-null mice of the same age contained fewer lipid droplets (Fig. 3h). In accordance with the lesser lipid content, the weight of the BAT from nine-month-old Cidea-null mice was 60% less than that of the wild-type mice (data not shown). The rapid depletion of lipid and decrease in fat accumu- lation in BAT were not due to greater lipase activity, as we detected no difference in hormone-sensitive lipase (HSL) activity between BAT from Cidea-null and wild-type mice ( Table ...

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Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies with poor prognosis and lack of effective targeted therapies. In this study, we investigated the tumor suppressive role of the cell death inducing DFF like effector A (CIDEA) in ESCC. Firstly, public datasets and ESCC tissue microarray analysis showed that CIDEA was frequently down-regulated at both the mRNA and protein level. This was significantly associated with low differentiation and TNM stage in ESCC, and indicated poor prognosis for ESCC patients. Bisulfite genomic sequencing (BGS) and methylation-specific PCR (MSP) analysis revealed that the down-regulation of CIDEA was associated with hypermethylation of its promoter, which was also correlated with the poor prognosis in ESCC patients. In vitro and in vivo functional studies demonstrated that CIDEA decreased cell growth, foci formation, DNA replication, and tumorigenesis in nude mice. Further study revealed that, during starvation or cisplatin induced DNA damage, CIDEA facilitated the G1-phase arrest or caspase-dependent mitochondrial apoptosis through the JNK-p21/Bad pathway. Therefore, CIDEA is a novel tumor suppressor gene that plays an important role in the development and progression of ESCC, and may provide a potential therapeutic target for patients with ESCC.