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Adipose hypothermia in obesity and its association with period homolog 1, insulin sensitivity, and inflammation in fat.

Yamaoka M, Maeda N, Takayama Y, Sekimoto R, Tsushima Y, Matsuda K, Mori T, Inoue K, Nishizawa H, Tominaga M, Funahashi T, Shimomura I - PLoS ONE (2014)

Bottom Line: Genes related to circadian rhythm were highly associated with visceral fat area and period homolog 1 (PER1) showed the most significant negative correlation with visceral fat area.However, no significant changes in Per1 mRNA level were observed by these agents.Exposure of cultured 3T3-L1 adipocytes to low temperature (33°C) decreased Per1 and catalase, and increased monocyte chemoattractant protein-1 (Mcp-1) mRNA levels.

View Article: PubMed Central - PubMed

Affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan.

ABSTRACT
Visceral fat adiposity plays an important role in the development of metabolic syndrome. We reported previously the impact of human visceral fat adiposity on gene expression profile of peripheral blood cells. Genes related to circadian rhythm were highly associated with visceral fat area and period homolog 1 (PER1) showed the most significant negative correlation with visceral fat area. However, regulation of adipose Per1 remains poorly understood. The present study was designed to understand the regulation of Per1 in adipose tissues. Adipose Per1 mRNA levels of ob/ob mice were markedly low at 25 and 35 weeks of age. The levels of other core clock genes of white adipose tissues were also low in ob/ob mice at 25 and 35 weeks of age. Per1 mRNA was mainly expressed in the mature adipocyte fraction (MAF) and it was significantly low in MAF of ob/ob mice. To examine the possible mechanisms, 3T3-L1 adipocytes were treated with H2O2, tumor necrosis factor-α (TNF-α), S100A8, and lipopolysaccharide (LPS). However, no significant changes in Per1 mRNA level were observed by these agents. Exposure of cultured 3T3-L1 adipocytes to low temperature (33°C) decreased Per1 and catalase, and increased monocyte chemoattractant protein-1 (Mcp-1) mRNA levels. Hypothermia also worsened insulin-mediated Akt phosphorylation in 3T3-L1 adipocytes. Finally, telemetric analysis showed low temperature of adipose tissues in ob/ob mice. In obesity, adipose hypothermia seems to accelerate adipocyte dysfunction.

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The mRNA expression levels of core clock genes.A to C, Comparison of core clock genes in the liver (A), muscle (B), and kidney (C) between C57BL/6N (B6) and ob/ob (ob) mice at 35 weeks of age. n = 3–8 per group. D, Per1 mRNA levels in mature adipocyte fraction (MAF) and stromal vascular fraction (SVF) of B6 and ob mice. WAT of 8-week-old mice was fractionated as described in Materials and Methods section. n = 6 per group. Values are mean ± SEM. **P<0.01; ***P<0.001. $$$P<0.001, compared to MAF of B6 mice. #P<0.05, compared to SVF of B6 mice.
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pone-0112813-g002: The mRNA expression levels of core clock genes.A to C, Comparison of core clock genes in the liver (A), muscle (B), and kidney (C) between C57BL/6N (B6) and ob/ob (ob) mice at 35 weeks of age. n = 3–8 per group. D, Per1 mRNA levels in mature adipocyte fraction (MAF) and stromal vascular fraction (SVF) of B6 and ob mice. WAT of 8-week-old mice was fractionated as described in Materials and Methods section. n = 6 per group. Values are mean ± SEM. **P<0.01; ***P<0.001. $$$P<0.001, compared to MAF of B6 mice. #P<0.05, compared to SVF of B6 mice.

Mentions: As shown in Figure 1, the levels of the majority of core clock genes decreased dynamically in WAT at late stage of obesity. Next, we measured the mRNA levels of these clock genes in other insulin-sensitive organs, such as the liver, skeletal muscles, and kidneys at 35 weeks of age. In the liver, Per1 mRNA level was slightly lower in ob/ob mice compared to B6 mice while the levels of other circadian genes were comparable in the two species (Figure 2A). In skeletal muscles, Clock mRNA level was lower in ob/ob compared with B6 mice, but there were no significant differences in other circadian clock genes between the two species (Figure 2B). In the kidney, Cry2 mRNA level was higher while Bmal1 and Clock mRNA levels were lower in ob/ob mice compared to B6 mice (Figure 2C). Per1, Per2, and Cry1 mRNA levels in the kidneys were similar in the two mice groups (Figure 2C). While the mRNA expression levels of several core clock genes in the liver, skeletal muscles, and kidneys varied between the two mice groups, the variability was much smaller, compared to those in WAT (compare Figures 2A–2C and 1B–1G).


Adipose hypothermia in obesity and its association with period homolog 1, insulin sensitivity, and inflammation in fat.

Yamaoka M, Maeda N, Takayama Y, Sekimoto R, Tsushima Y, Matsuda K, Mori T, Inoue K, Nishizawa H, Tominaga M, Funahashi T, Shimomura I - PLoS ONE (2014)

The mRNA expression levels of core clock genes.A to C, Comparison of core clock genes in the liver (A), muscle (B), and kidney (C) between C57BL/6N (B6) and ob/ob (ob) mice at 35 weeks of age. n = 3–8 per group. D, Per1 mRNA levels in mature adipocyte fraction (MAF) and stromal vascular fraction (SVF) of B6 and ob mice. WAT of 8-week-old mice was fractionated as described in Materials and Methods section. n = 6 per group. Values are mean ± SEM. **P<0.01; ***P<0.001. $$$P<0.001, compared to MAF of B6 mice. #P<0.05, compared to SVF of B6 mice.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4232416&req=5

pone-0112813-g002: The mRNA expression levels of core clock genes.A to C, Comparison of core clock genes in the liver (A), muscle (B), and kidney (C) between C57BL/6N (B6) and ob/ob (ob) mice at 35 weeks of age. n = 3–8 per group. D, Per1 mRNA levels in mature adipocyte fraction (MAF) and stromal vascular fraction (SVF) of B6 and ob mice. WAT of 8-week-old mice was fractionated as described in Materials and Methods section. n = 6 per group. Values are mean ± SEM. **P<0.01; ***P<0.001. $$$P<0.001, compared to MAF of B6 mice. #P<0.05, compared to SVF of B6 mice.
Mentions: As shown in Figure 1, the levels of the majority of core clock genes decreased dynamically in WAT at late stage of obesity. Next, we measured the mRNA levels of these clock genes in other insulin-sensitive organs, such as the liver, skeletal muscles, and kidneys at 35 weeks of age. In the liver, Per1 mRNA level was slightly lower in ob/ob mice compared to B6 mice while the levels of other circadian genes were comparable in the two species (Figure 2A). In skeletal muscles, Clock mRNA level was lower in ob/ob compared with B6 mice, but there were no significant differences in other circadian clock genes between the two species (Figure 2B). In the kidney, Cry2 mRNA level was higher while Bmal1 and Clock mRNA levels were lower in ob/ob mice compared to B6 mice (Figure 2C). Per1, Per2, and Cry1 mRNA levels in the kidneys were similar in the two mice groups (Figure 2C). While the mRNA expression levels of several core clock genes in the liver, skeletal muscles, and kidneys varied between the two mice groups, the variability was much smaller, compared to those in WAT (compare Figures 2A–2C and 1B–1G).

Bottom Line: Genes related to circadian rhythm were highly associated with visceral fat area and period homolog 1 (PER1) showed the most significant negative correlation with visceral fat area.However, no significant changes in Per1 mRNA level were observed by these agents.Exposure of cultured 3T3-L1 adipocytes to low temperature (33°C) decreased Per1 and catalase, and increased monocyte chemoattractant protein-1 (Mcp-1) mRNA levels.

View Article: PubMed Central - PubMed

Affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan.

ABSTRACT
Visceral fat adiposity plays an important role in the development of metabolic syndrome. We reported previously the impact of human visceral fat adiposity on gene expression profile of peripheral blood cells. Genes related to circadian rhythm were highly associated with visceral fat area and period homolog 1 (PER1) showed the most significant negative correlation with visceral fat area. However, regulation of adipose Per1 remains poorly understood. The present study was designed to understand the regulation of Per1 in adipose tissues. Adipose Per1 mRNA levels of ob/ob mice were markedly low at 25 and 35 weeks of age. The levels of other core clock genes of white adipose tissues were also low in ob/ob mice at 25 and 35 weeks of age. Per1 mRNA was mainly expressed in the mature adipocyte fraction (MAF) and it was significantly low in MAF of ob/ob mice. To examine the possible mechanisms, 3T3-L1 adipocytes were treated with H2O2, tumor necrosis factor-α (TNF-α), S100A8, and lipopolysaccharide (LPS). However, no significant changes in Per1 mRNA level were observed by these agents. Exposure of cultured 3T3-L1 adipocytes to low temperature (33°C) decreased Per1 and catalase, and increased monocyte chemoattractant protein-1 (Mcp-1) mRNA levels. Hypothermia also worsened insulin-mediated Akt phosphorylation in 3T3-L1 adipocytes. Finally, telemetric analysis showed low temperature of adipose tissues in ob/ob mice. In obesity, adipose hypothermia seems to accelerate adipocyte dysfunction.

Show MeSH
Related in: MedlinePlus