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Cyclin Y Is Involved in the Regulation of Adipogenesis and Lipid Production.

An W, Zhang Z, Zeng L, Yang Y, Zhu X, Wu J - PLoS ONE (2015)

Bottom Line: A new member of the cyclin family cyclin Y (CCNY) is involved in the regulation of various physiological processes.In this study, the role of CCNY in energy metabolism was characterized.The hepatic insulin resistance generated by Ccny depletion resulted in down-regulation of the sterol-regulatory element-binding protein (SREBP1) and fatty acid synthase (FASN).

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.

ABSTRACT
A new member of the cyclin family cyclin Y (CCNY) is involved in the regulation of various physiological processes. In this study, the role of CCNY in energy metabolism was characterized. We found that compared with wild-type (WT) mice, Ccny knockout (KO) mice had both lower body weight and lower fat content. The Ccny KO mice also had a higher metabolic rate, resisted the stress of a high-fat diet, and were sensitive to calorie restriction. The expression levels of UCP1 and PGC1α were significantly higher in the brown adipose tissue (BAT) of the Ccny KO mice than that of the WT littermate controls, whereas there was no significant difference in BAT weight between the WT and the Ccny KO mice. In addition, the down-regulation of Ccny resulted in suppression of white adipocyte differentiation both in vivo and in vitro, while the expression of Ccny was up-regulated by C/EBPα. Furthermore, both hepatocytes and HepG2 cells that were depleted of Ccny were insensitive to insulin stimulation, consistent with the significant inhibition of insulin sensitivity in the liver of the Ccny KO mice, but no significant changes in WAT and muscle, indicating that CCNY is involved in regulating the hepatic insulin signaling pathway. The hepatic insulin resistance generated by Ccny depletion resulted in down-regulation of the sterol-regulatory element-binding protein (SREBP1) and fatty acid synthase (FASN). Together, these results provide a new link between CCNY and lipid metabolism in mice, and suggest that inhibition of CCNY may offer a therapeutic approach to obesity and diabetes.

No MeSH data available.


Related in: MedlinePlus

Ccny KO mice are resistant to a high-fat diet (HFD) and sensitive to calorie restriction.The mice received either HFD or calorie restriction. (A) The body weight curve of 8-week-old mice treated with 12 weeks HFD (n = 6–7 males per genotype). (B) Body fat contents of the 12-week-HFD mice (n = 6–7 males per genotype). Body fat content: retroperitoneal fat (retroperi), inguinal fat, periadrenal fat and armpit fat. (C) The fasting plasma levels of the triglycerides, cholesterol, free fatty acids (FFAs) were measured in 12-week-HFD mice (n = 6–7 males per genotype). (D-F) The mice were treated with calorie restriction. (D) The body weights of 13-week-old mice treated with a 10% reduced food intake were measured at the indicated times (n = 6–8 males per genotype); (E) Body fat contents (n = 6–8 males per genotype); (F) Fasting plasma levels of triglycerides, cholesterol, and free fatty acids (FFAs) (n = 6–8 males per genotype). *, P<0.05; **, P<0.01 WT vs Ccny KO. Error bars, S. E.
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pone.0132721.g003: Ccny KO mice are resistant to a high-fat diet (HFD) and sensitive to calorie restriction.The mice received either HFD or calorie restriction. (A) The body weight curve of 8-week-old mice treated with 12 weeks HFD (n = 6–7 males per genotype). (B) Body fat contents of the 12-week-HFD mice (n = 6–7 males per genotype). Body fat content: retroperitoneal fat (retroperi), inguinal fat, periadrenal fat and armpit fat. (C) The fasting plasma levels of the triglycerides, cholesterol, free fatty acids (FFAs) were measured in 12-week-HFD mice (n = 6–7 males per genotype). (D-F) The mice were treated with calorie restriction. (D) The body weights of 13-week-old mice treated with a 10% reduced food intake were measured at the indicated times (n = 6–8 males per genotype); (E) Body fat contents (n = 6–8 males per genotype); (F) Fasting plasma levels of triglycerides, cholesterol, and free fatty acids (FFAs) (n = 6–8 males per genotype). *, P<0.05; **, P<0.01 WT vs Ccny KO. Error bars, S. E.

Mentions: We expected that the Ccny KO mice and the WT controls would respond differently to energetic stresses. The mice were first subjected to a HFD. The body weight of the Ccny KO mice was lower than that of the WT control mice on the HFD (Fig 3A and S3A Fig). The body fat contents in the Ccny KO mice, including the retroperitoneal, inguinal, perirenal and armpit fat pads, were also smaller than that in the WT control mice under such treatments (Fig 3B and S3B Fig). In addition, the Ccny KO mice had greater variations in their triglyceride, total plasma cholesterol and free fatty acid levels compared with those of the WT controls (Fig 3C). These results suggest that the Ccny KO mice were resistant to the HFD treatment.


Cyclin Y Is Involved in the Regulation of Adipogenesis and Lipid Production.

An W, Zhang Z, Zeng L, Yang Y, Zhu X, Wu J - PLoS ONE (2015)

Ccny KO mice are resistant to a high-fat diet (HFD) and sensitive to calorie restriction.The mice received either HFD or calorie restriction. (A) The body weight curve of 8-week-old mice treated with 12 weeks HFD (n = 6–7 males per genotype). (B) Body fat contents of the 12-week-HFD mice (n = 6–7 males per genotype). Body fat content: retroperitoneal fat (retroperi), inguinal fat, periadrenal fat and armpit fat. (C) The fasting plasma levels of the triglycerides, cholesterol, free fatty acids (FFAs) were measured in 12-week-HFD mice (n = 6–7 males per genotype). (D-F) The mice were treated with calorie restriction. (D) The body weights of 13-week-old mice treated with a 10% reduced food intake were measured at the indicated times (n = 6–8 males per genotype); (E) Body fat contents (n = 6–8 males per genotype); (F) Fasting plasma levels of triglycerides, cholesterol, and free fatty acids (FFAs) (n = 6–8 males per genotype). *, P<0.05; **, P<0.01 WT vs Ccny KO. Error bars, S. E.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4498623&req=5

pone.0132721.g003: Ccny KO mice are resistant to a high-fat diet (HFD) and sensitive to calorie restriction.The mice received either HFD or calorie restriction. (A) The body weight curve of 8-week-old mice treated with 12 weeks HFD (n = 6–7 males per genotype). (B) Body fat contents of the 12-week-HFD mice (n = 6–7 males per genotype). Body fat content: retroperitoneal fat (retroperi), inguinal fat, periadrenal fat and armpit fat. (C) The fasting plasma levels of the triglycerides, cholesterol, free fatty acids (FFAs) were measured in 12-week-HFD mice (n = 6–7 males per genotype). (D-F) The mice were treated with calorie restriction. (D) The body weights of 13-week-old mice treated with a 10% reduced food intake were measured at the indicated times (n = 6–8 males per genotype); (E) Body fat contents (n = 6–8 males per genotype); (F) Fasting plasma levels of triglycerides, cholesterol, and free fatty acids (FFAs) (n = 6–8 males per genotype). *, P<0.05; **, P<0.01 WT vs Ccny KO. Error bars, S. E.
Mentions: We expected that the Ccny KO mice and the WT controls would respond differently to energetic stresses. The mice were first subjected to a HFD. The body weight of the Ccny KO mice was lower than that of the WT control mice on the HFD (Fig 3A and S3A Fig). The body fat contents in the Ccny KO mice, including the retroperitoneal, inguinal, perirenal and armpit fat pads, were also smaller than that in the WT control mice under such treatments (Fig 3B and S3B Fig). In addition, the Ccny KO mice had greater variations in their triglyceride, total plasma cholesterol and free fatty acid levels compared with those of the WT controls (Fig 3C). These results suggest that the Ccny KO mice were resistant to the HFD treatment.

Bottom Line: A new member of the cyclin family cyclin Y (CCNY) is involved in the regulation of various physiological processes.In this study, the role of CCNY in energy metabolism was characterized.The hepatic insulin resistance generated by Ccny depletion resulted in down-regulation of the sterol-regulatory element-binding protein (SREBP1) and fatty acid synthase (FASN).

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.

ABSTRACT
A new member of the cyclin family cyclin Y (CCNY) is involved in the regulation of various physiological processes. In this study, the role of CCNY in energy metabolism was characterized. We found that compared with wild-type (WT) mice, Ccny knockout (KO) mice had both lower body weight and lower fat content. The Ccny KO mice also had a higher metabolic rate, resisted the stress of a high-fat diet, and were sensitive to calorie restriction. The expression levels of UCP1 and PGC1α were significantly higher in the brown adipose tissue (BAT) of the Ccny KO mice than that of the WT littermate controls, whereas there was no significant difference in BAT weight between the WT and the Ccny KO mice. In addition, the down-regulation of Ccny resulted in suppression of white adipocyte differentiation both in vivo and in vitro, while the expression of Ccny was up-regulated by C/EBPα. Furthermore, both hepatocytes and HepG2 cells that were depleted of Ccny were insensitive to insulin stimulation, consistent with the significant inhibition of insulin sensitivity in the liver of the Ccny KO mice, but no significant changes in WAT and muscle, indicating that CCNY is involved in regulating the hepatic insulin signaling pathway. The hepatic insulin resistance generated by Ccny depletion resulted in down-regulation of the sterol-regulatory element-binding protein (SREBP1) and fatty acid synthase (FASN). Together, these results provide a new link between CCNY and lipid metabolism in mice, and suggest that inhibition of CCNY may offer a therapeutic approach to obesity and diabetes.

No MeSH data available.


Related in: MedlinePlus