Skp2 controls adipocyte proliferation during the development of obesity

Tamon Sakai, Hiroshi Sakaue, Takehiro Nakamura, Mitsuru Okada, Yasushi Matsuki, Eijiro Watanabe, Ryuji Hiramatsu, Keiko Nakayama, Keiichi Nakayama, Masato Kasuga

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

The increase in the mass of adipose tissue during the development of obesity can arise through an increase in cell size, an increase in cell number, or both. Here we show that long term maintenance of C57BL/6 mice on a high fat diet (for ∼25 weeks) induces an initial increase in adipocyte size followed by an increase in adipocyte number in white adipose tissue. The latter effect was found to be accompanied by up-regulation of expression of the gene for the F-box protein Skp2 as well as by down-regulation of the cyclin-dependent kinase inhibitor p27Kip1, a principal target of the SCFSkp2 ubiquitin ligase, in white adipose tissue. Ablation of Skp2 protected mice from the development of obesity induced either by a high fat diet or by the lethal yellow agouti (Ay) mutation, and this protective action was due to inhibition of the increase in adipocyte number without an effect on adipocyte hypertrophy. The reduction in the number of adipocyte caused by Skp2 ablation also inhibited the development of obesity-related insulin resistance in the Ay mutant mice, although the reduced number of β cells and reduced level of insulin secretion in Skp2-deficient mice resulted in glucose intolerance. Our observations thus indicate that Skp2 controls adipocyte proliferation during the development of obesity.

Original languageEnglish
Pages (from-to)2038-2046
Number of pages9
JournalJournal of Biological Chemistry
Volume282
Issue number3
DOIs
Publication statusPublished - Jan 19 2007

Fingerprint

Adipocytes
Obesity
Tissue
Nutrition
Ablation
Fats
F-Box Proteins
Insulin
White Adipose Tissue
Cyclin-Dependent Kinases
High Fat Diet
Ligases
Ubiquitin
Cell Count
Genes
Glucose
Glucose Intolerance
Inbred C57BL Mouse
Cell Size
Hypertrophy

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Sakai, T., Sakaue, H., Nakamura, T., Okada, M., Matsuki, Y., Watanabe, E., ... Kasuga, M. (2007). Skp2 controls adipocyte proliferation during the development of obesity. Journal of Biological Chemistry, 282(3), 2038-2046. https://doi.org/10.1074/jbc.M608144200

Skp2 controls adipocyte proliferation during the development of obesity. / Sakai, Tamon; Sakaue, Hiroshi; Nakamura, Takehiro; Okada, Mitsuru; Matsuki, Yasushi; Watanabe, Eijiro; Hiramatsu, Ryuji; Nakayama, Keiko; Nakayama, Keiichi; Kasuga, Masato.

In: Journal of Biological Chemistry, Vol. 282, No. 3, 19.01.2007, p. 2038-2046.

Research output: Contribution to journalArticle

Sakai, T, Sakaue, H, Nakamura, T, Okada, M, Matsuki, Y, Watanabe, E, Hiramatsu, R, Nakayama, K, Nakayama, K & Kasuga, M 2007, 'Skp2 controls adipocyte proliferation during the development of obesity', Journal of Biological Chemistry, vol. 282, no. 3, pp. 2038-2046. https://doi.org/10.1074/jbc.M608144200
Sakai T, Sakaue H, Nakamura T, Okada M, Matsuki Y, Watanabe E et al. Skp2 controls adipocyte proliferation during the development of obesity. Journal of Biological Chemistry. 2007 Jan 19;282(3):2038-2046. https://doi.org/10.1074/jbc.M608144200
Sakai, Tamon ; Sakaue, Hiroshi ; Nakamura, Takehiro ; Okada, Mitsuru ; Matsuki, Yasushi ; Watanabe, Eijiro ; Hiramatsu, Ryuji ; Nakayama, Keiko ; Nakayama, Keiichi ; Kasuga, Masato. / Skp2 controls adipocyte proliferation during the development of obesity. In: Journal of Biological Chemistry. 2007 ; Vol. 282, No. 3. pp. 2038-2046.
@article{c9264bdc30844faf98d770ded18cf051,
title = "Skp2 controls adipocyte proliferation during the development of obesity",
abstract = "The increase in the mass of adipose tissue during the development of obesity can arise through an increase in cell size, an increase in cell number, or both. Here we show that long term maintenance of C57BL/6 mice on a high fat diet (for ∼25 weeks) induces an initial increase in adipocyte size followed by an increase in adipocyte number in white adipose tissue. The latter effect was found to be accompanied by up-regulation of expression of the gene for the F-box protein Skp2 as well as by down-regulation of the cyclin-dependent kinase inhibitor p27Kip1, a principal target of the SCFSkp2 ubiquitin ligase, in white adipose tissue. Ablation of Skp2 protected mice from the development of obesity induced either by a high fat diet or by the lethal yellow agouti (Ay) mutation, and this protective action was due to inhibition of the increase in adipocyte number without an effect on adipocyte hypertrophy. The reduction in the number of adipocyte caused by Skp2 ablation also inhibited the development of obesity-related insulin resistance in the Ay mutant mice, although the reduced number of β cells and reduced level of insulin secretion in Skp2-deficient mice resulted in glucose intolerance. Our observations thus indicate that Skp2 controls adipocyte proliferation during the development of obesity.",
author = "Tamon Sakai and Hiroshi Sakaue and Takehiro Nakamura and Mitsuru Okada and Yasushi Matsuki and Eijiro Watanabe and Ryuji Hiramatsu and Keiko Nakayama and Keiichi Nakayama and Masato Kasuga",
year = "2007",
month = "1",
day = "19",
doi = "10.1074/jbc.M608144200",
language = "English",
volume = "282",
pages = "2038--2046",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "3",

}

TY - JOUR

T1 - Skp2 controls adipocyte proliferation during the development of obesity

AU - Sakai, Tamon

AU - Sakaue, Hiroshi

AU - Nakamura, Takehiro

AU - Okada, Mitsuru

AU - Matsuki, Yasushi

AU - Watanabe, Eijiro

AU - Hiramatsu, Ryuji

AU - Nakayama, Keiko

AU - Nakayama, Keiichi

AU - Kasuga, Masato

PY - 2007/1/19

Y1 - 2007/1/19

N2 - The increase in the mass of adipose tissue during the development of obesity can arise through an increase in cell size, an increase in cell number, or both. Here we show that long term maintenance of C57BL/6 mice on a high fat diet (for ∼25 weeks) induces an initial increase in adipocyte size followed by an increase in adipocyte number in white adipose tissue. The latter effect was found to be accompanied by up-regulation of expression of the gene for the F-box protein Skp2 as well as by down-regulation of the cyclin-dependent kinase inhibitor p27Kip1, a principal target of the SCFSkp2 ubiquitin ligase, in white adipose tissue. Ablation of Skp2 protected mice from the development of obesity induced either by a high fat diet or by the lethal yellow agouti (Ay) mutation, and this protective action was due to inhibition of the increase in adipocyte number without an effect on adipocyte hypertrophy. The reduction in the number of adipocyte caused by Skp2 ablation also inhibited the development of obesity-related insulin resistance in the Ay mutant mice, although the reduced number of β cells and reduced level of insulin secretion in Skp2-deficient mice resulted in glucose intolerance. Our observations thus indicate that Skp2 controls adipocyte proliferation during the development of obesity.

AB - The increase in the mass of adipose tissue during the development of obesity can arise through an increase in cell size, an increase in cell number, or both. Here we show that long term maintenance of C57BL/6 mice on a high fat diet (for ∼25 weeks) induces an initial increase in adipocyte size followed by an increase in adipocyte number in white adipose tissue. The latter effect was found to be accompanied by up-regulation of expression of the gene for the F-box protein Skp2 as well as by down-regulation of the cyclin-dependent kinase inhibitor p27Kip1, a principal target of the SCFSkp2 ubiquitin ligase, in white adipose tissue. Ablation of Skp2 protected mice from the development of obesity induced either by a high fat diet or by the lethal yellow agouti (Ay) mutation, and this protective action was due to inhibition of the increase in adipocyte number without an effect on adipocyte hypertrophy. The reduction in the number of adipocyte caused by Skp2 ablation also inhibited the development of obesity-related insulin resistance in the Ay mutant mice, although the reduced number of β cells and reduced level of insulin secretion in Skp2-deficient mice resulted in glucose intolerance. Our observations thus indicate that Skp2 controls adipocyte proliferation during the development of obesity.

UR - http://www.scopus.com/inward/record.url?scp=33847250516&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33847250516&partnerID=8YFLogxK

U2 - 10.1074/jbc.M608144200

DO - 10.1074/jbc.M608144200

M3 - Article

C2 - 17082193

AN - SCOPUS:33847250516

VL - 282

SP - 2038

EP - 2046

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 3

ER -